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To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as high-content screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner.
Two-dimensional formulations for wind forces on elongated bodies, such as bridge decks, are reviewed and links with expressions found in two-dimensional airfoil theory are pointed out. The present research focus on indicial lift responses and admittance functions which are commonly used to improve buffeting analysis of bluff bodies. A computational fluid dynamic (CFD) analysis is used to derive these aerodynamic functions for various sections. The numerical procedure is presented and results are discussed which demonstrate that the particular shapes of these functions are strongly dependent on the evolution of the separated flows around the sections at the early stages.
The disintegration of the USSR in the early 1990s created fifteen new nation-states. Among these were five former Soviet republics of Central Asia-Kazakstan, Kyrgyzstan, Takikistan, Turkmenistan, and Uzbekistan. These entities existed for decades as administrative jurisdictions within the Soviet Union but never exercised the authonomy of true states. Prior to the Soviet period, none of them had existed as independent countries; furthermore, they shared the ties of tradition, history, language, culture, and a common administrative system. Yet the dynamics f independence has propelled them in different and sometimes conflicting directions. The politics and economics of decolonization are exerting a continuing influence on these countries, affecting the way in which they relate to one another and to the outside world. This article surveys the news Central Asian states, comparatively analyzes the circumstances of independence and decolonization, and draws conclusions regarding integration with greater Asia.
This paper provides some general background on New Zealand society, government and politics, before outlining the economic and governmental policy revolution of the 1980s and early 1990s, which saw radical changes made to the structure and processes of central government administration. Public administration was transmogrified into public management and state bureaucracies were required to carry out their work in a much more efficient and accountable way, to be more ``businesslike``. Since then some deficiencies arising out of the reforms have become apparent. These include the possible attenuation of the public service ethos, too great a preoccupation with the production of outputs, insufficient collaborative activity on the part of government departments in pursuit of strategic policy outcomes, the problematic accountability of agencies that exist outside of the core Public Service, and the threat of diminished executive and managerial capability in the system. Legislation passed by Parliament in late 2004 has been designed to overcome these difficulties. The paper outlines the provisions of this legislation. It raises some questions about its likely efficacy, and concludes with a discussion of some other central issues arising out of the New Zealand experience of state sector reform - the underlying problem of the outputs/outcomes bifurcation, changing political-bureaucratic realities, the state-citizen relationship, and theory and pragmatism in governmental reorganization.
이 논문의 목적은 미국에서 행해 왔던 두 가지의 기본적인 성교육의 방법들을 살펴보고, 미래에 있어서는 어느 방향으로 나가야 할 것인가를 보기 위해 그 방법들을 통일사상의 교육론적 관점에서 평가하려 하는 것이다. 누구라도 이 폭발물과도 같이 위험한 주제에 내포되어 있는 육체적, 심리적 위험성을 깨닫기만 한다면, 그는 이 주제가 미국의 차원에서뿐 아니라 전 세계적으로도 중요하다는 것을 알 수 있을 것이다. This article presents the problem solving strategy for predicting the types of binary azeotropes in a hierarchical knowledge-based expert system, AZEOPERT. The use of expert system concepts is examined to develop a consultant for predicting the types of binary azeotropes in organic mixtures; especially the binary systems that until now have been not reported. The knowledge base for the prediction of the types of binary azeotropes consists of two levels of domain-specific heuristics structured hierarchically. The predictive capabilities and generality of AZEOPERT can be highly enhanced through the integration of different kinds of domain knowledge into the hierarchical structure. AZEOPERT has been implemented with the artificial intelligence programming language IF/Prolog, developed in a UNIX environment. About 60 heuristic rules for predicting the types of binary azeotrope have been implemented in AZEOPERT. The required input data for consultation are only names of homologous groups or occasionally, class names, classified by the tendency of hydrogen bondings for consulted binary components which can usually be provided easily. The heuristic rules in each level were formulated by a combination of theoretical considerations, practical experience, and case studies through a binary azeotropic data bank. Prediction of the types of binary azeotropes using AZEOPERT may give chemical engineers a good contribution to perform the process synthesis, moreover, to select the proper separating agents for separation processes and the proper refrigerants in the area of air conditioning and refrigeration.
In the wake of the Arab Spring, the Internet's role in aiding dramatic political transformation has come to the fore. Throughout the Middle East, protestors have employed Facebook, Twitter, Youtube and other popular websites to organize and spread news at home and to the outside world. Chinese authorities have been increasingly nervous about the Arab uprisings, and fear that similar events will inspire unrest in China. The new information and communication technologies make it possible for social movements to initiate novel forms of collective actions. The Internet provides new opportunities for political liberalization. In Chinese society, citizens can now participate in politics uninvited. With each passing day, the online community gets stronger. The digital revolution has the potential for broadening democratic principles and could bring democracy to the collective Chinese mind.