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31.
B L Stoddard  D E Koshland 《Nature》1992,358(6389):774-776
To validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein-protein and peptide-protein interactions has been sparse. We were able to test such applications once the structures of both the maltose-binding protein (MBP) and the ligand-binding domain of the aspartate receptor, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP-receptor complex. The consistency of the computational and biological results supports this approach for predicting protein-protein and peptide-protein interactions.  相似文献   
32.
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.  相似文献   
33.
Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1.  相似文献   
34.
利用一个固定的抛物型M bius变换作为检验性元素来检验扩充复平面上的非初等M bius群的离散性 ,文中给出的结果改进了由Jrgensen所建立的判别准则  相似文献   
35.
This paper is a case study about how a new product developed by Western multinational company enters new market ?the Mainland China. In this study, a new fabric ?DuPont's hi-technical Tyvek?PU Coating, is fashionized and developed into a new fashionable and functional casual-rainwear, using the approach of new product development method ( idea generation; screening; business analysis; development; evaluation and testing; commercialization).  相似文献   
36.
Summary Immunohistochemistry revealed an Ig-A-like substance on the luminal surface of the pineal follicles and in the parafollicular layer. This substance was observed around 1 week of age and disappeared by 8 weeks at the time when the transformation of the follicular pattern leads to an adult-type pineal tissue.  相似文献   
37.
Product data management (PDM) has been accepted as an important tool for the manufacturing industries. In recent years, more and mor e researches have been conducted in the development of PDM. Their research area s include system design, integration of object-oriented technology, data distri bution, collaborative and distributed manufacturing working environment, secur ity, and web-based integration. However, there are limitations on their rese arches. In particular, they cannot cater for PDM in dis...  相似文献   
38.
本文从当代设计所面临的严峻挑战出发,回顾设计方法学的崛起,综述了在设计及设计方法学研究方面,主要发达国家采取的措施及主要专家、学者的贡献和成就。指出:设计必须科学化,而设计方法学研究是设计走向科学化的重要一步;必须加强对设计本身的研究;计算机技术在设计领域中的应用及其与设计理论研究的结合,对设计的发展及科学化将具有特别重要的意义。  相似文献   
39.
本文用粘弹谱仪、x射线衍射、DSC研究了PET—云母复合物的Tg区域的多重转变等松驰转变行为,探讨了加工、云母填充对PET—云母材料性能影响的分子运动机理。不同热历史(如不同成型条件、热处理等)使聚合物分子形成不同链段运动;处于高温位的Tg(u)其运动单元是受结晶、内应力、填料作用影响的非晶区链段。  相似文献   
40.
本文采用固定高速摄影及影片数字化研究方法,对山西体操运动员郭佳在1990年新创的屈体腾越转体180°再握动作进行运动学分析,得出各技术环节的运动学数据,找到其动作的运动学特征,为我国体操教练员和运动员提供参考。  相似文献   
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