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41.
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   
42.
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   
43.
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   
44.
科技论文摘要的写作   总被引:1,自引:0,他引:1  
科技论文摘要作为二次文献,具有举要性、示导性、贮存性、传扬性及商品性等功能,具有客观性、说明性、简练性等特征;摘要的写作要求是以精练的文字高度概括地反映论文的主题、结论及有关实质性信息。在内容在述与文字长短允许的情况下,尽可能运用报道性或报道-指示性文体;要保证摘要的独立性、自含性和完整性。  相似文献   
45.
本文在样本序列{(X_n,Y_n),n≥1}为φ-混合的,平稳的情形下讨论了回归函数m(x)的最近邻估计m_n(x)的L_p相合性和强相合性,并给出了它在非参数k_n-NN判别中的一个应用。  相似文献   
46.
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   
47.
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   
48.
非惯性系内的气体浮力问题   总被引:1,自引:0,他引:1  
宋兆丽  孙石 《松辽学刊》1997,(3):55-56,64
本文研究了气体浮力的产生机制,并且重点讨论了非惯性系内的气体浮力问题,给出了有关计算公式。  相似文献   
49.
基于LDAP协议实现统一的网络管理研究   总被引:2,自引:0,他引:2  
基于网络上信息存储方式的不统一及其所面临的困难 ,结合复旦大学校园网的特点 ,在深入研究LDAP协议的基础上 ,给出了一套跨协议认证的解决方案 ,提出了关于同步问题的两个模型和基于CSN方法的实现办法  相似文献   
50.
伪随机序列生成方法有很多种 ,因生成方法不同而导致其性质的差异较大 .文中描述了产生均匀分布的U (0 ,1 )伪随机序列的数学原理 ,提出了评估均匀分布伪随机序列均匀性的几种方法 ,对由软件产生的几种均匀分布序列的均匀性作出了评估  相似文献   
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