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Smith, A.S.T.,Davis, J.,Lee, G.,Mack, D.L.,Kim, D.H. Elsevier Science Ltd ; Distributed by Virgin Maili 2016 DRUG DISCOVERY TODAY Vol.21 No.9
Engineered in vitro models using human cells, particularly patient-derived induced pluripotent stem cells (iPSCs), offer a potential solution to issues associated with the use of animals for studying disease pathology and drug efficacy. Given the prevalence of muscle diseases in human populations, an engineered tissue model of human skeletal muscle could provide a biologically accurate platform to study basic muscle physiology, disease progression, and drug efficacy and/or toxicity. Such platforms could be used as phenotypic drug screens to identify compounds capable of alleviating or reversing congenital myopathies, such as Duchene muscular dystrophy (DMD). Here, we review current skeletal muscle modeling technologies with a specific focus on efforts to generate biomimetic systems for investigating the pathophysiology of dystrophic muscle.
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Metabolic engineering of microorganisms: general strategies and drug production
Lee, S.Y.,Kim, H.U.,Park, J.H.,Park, J.M.,Kim, T.Y. Elsevier Science Ltd ; Distributed by Virgin Maili 2009 DRUG DISCOVERY TODAY Vol.14 No.1
Many drugs and drug precursors found in natural organisms are rather difficult to synthesize chemically and to extract in large amounts. Metabolic engineering is playing an increasingly important role in the production of these drugs and drug precursors. This is typically achieved by establishing new metabolic pathways leading to the product formation, and enforcing or removing the existing metabolic pathways toward enhanced product formation. Recent advances in system biology and synthetic biology are allowing us to perform metabolic engineering at the whole cell level, thus enabling optimal design of a microorganism for the efficient production of drugs and drug precursors. In this review, we describe the general strategies for the metabolic engineering of microorganisms for the production of drugs and drug precursors. As successful examples of metabolic engineering, the approaches taken toward strain development for the production of artemisinin, an antimalarial drug, and benzylisoquinoline alkaloids, a family of antibacterial and anticancer drugs, are described in detail. Also, systems metabolic engineering of Escherichia coli for the production of l-valine, an important drug precursor, is showcased as an important strategy of future metabolic engineering effort.
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Diverse roles of the scaffolding protein RanBPM
Suresh, B.,Ramakrishna, S.,Baek, K.H. Elsevier Science Ltd ; Distributed by Virgin Maili 2012 Drug Discovery Today Vol. No.
Ran-binding protein microtubule-organizing center (RanBPM) appears to function as a scaffolding protein in several signal transduction pathways. RanBPM is a crucial component of multiprotein complexes that regulate the cellular function by modulating and/or assembling with a wide range of proteins in different intracellular regions and thereby mediate diverse cellular functions. This suggests a role for RanBPM as a scaffolding protein. In this article, we have summarized the diverse functions of RanBPM and its interacting partners that have been investigated to date. Also, we have categorized the role of RanBPM into four divisions: RanBPM as a modulator/protein stabilizer, regulator of transcription activity, cell cycle and neurological functions.
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