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Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.  相似文献   
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Hirota T  Lipp JJ  Toh BH  Peters JM 《Nature》2005,438(7071):1176-1180
Histones are subject to numerous post-translational modifications. Some of these 'epigenetic' marks recruit proteins that modulate chromatin structure. For example, heterochromatin protein 1 (HP1) binds to histone H3 when its lysine 9 residue has been tri-methylated by the methyltransferase Suv39h (refs 2-6). During mitosis, H3 is also phosphorylated by the kinase Aurora B. Although H3 phosphorylation is a hallmark of mitosis, its function remains mysterious. It has been proposed that histone phosphorylation controls the binding of proteins to chromatin, but any such mechanisms are unknown. Here we show that antibodies against mitotic chromosomal antigens that are associated with human autoimmune diseases specifically recognize H3 molecules that are modified by both tri-methylation of lysine 9 and phosphorylation of serine 10 (H3K9me3S10ph). The generation of H3K9me3S10ph depends on Suv39h and Aurora B, and occurs at pericentric heterochromatin during mitosis in different eukaryotes. Most HP1 typically dissociates from chromosomes during mitosis, but if phosphorylation of H3 serine 10 is inhibited, HP1 remains chromosome-bound throughout mitosis. H3 phosphorylation by Aurora B is therefore part of a 'methyl/phos switch' mechanism that displaces HP1 and perhaps other proteins from mitotic heterochromatin.  相似文献   
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Much data such as geometric image data and drawings have graph structures. Such data are called graph structured data. In order to manage efficiently such graph structured data, we need to analyze and abstract graph structures of such data. The purpose of this paper is to find knowledge representations which indicate plural abstractions of graph structured data. Firstly, we introduce a term graph as a graph pattern having structural variables,and a substitution over term graphs which is graph rewriting system. Next,for a graph G,we define a multiple layer (g,(θ1, …,θk)) of G as a pair of a term graph g and a list of 4 substitutionsθ1, …,θk such that G can be obtained from g by applying substitutions θ1, …,θk to g. In the same way,for a set S of graphs, we also define a multiple layer for Sas a pair (D,@) of a set 5 of term graphs and a list 6 of substitutions. Secondly,for a graph G and a set S of graphs,we present effective algorithms for extracting minimal multiple layers of G and S which give us stratifying abstractions of G and S,respectively. Finally,we report experimental results obtained by applying our algorithms to both artificial data and drawings of power plants which are real world data.  相似文献   
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InxGa1-xSb晶体是吸收波长可以在1.7–6.8μm范围内调控的三元半导体晶体,在红外探测、热光伏电池领域具有重要的应用前景,但由于其固液相线相距很远,容易形成成分偏析和结晶缺陷,且重力对流会增加晶体生长界面处物质输送的不均匀性,使得地面环境下难于生长高质量的InxGa1-xSb晶体.微重力环境由于抑制了自然对流,为晶体生长提供了良好条件,本文综述了微重力环境对InxGa1-xSb半导体晶体成分偏析和晶体缺陷的影响,并介绍了中国返回式微重力科学卫星实践十号上的InxGa1-xSb三元晶体的空间生长实验成果.  相似文献   
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Summary Chlamydocin, a potent cytostatic agent against cultured mammalian cells, and HC-toxin, a host-specific phytotoxin, are cyclic tetrapeptides containing the same epoxide -amino acid. We show here that these compounds have reciprocal biological activity; HC-toxin is cytostatic against cultured mastocytoma cells, and chlamydocin has host-specific toxin activity against maize. Chlamydocin and another related cyclic peptide, Cyl-2, are less host-specific than HC-toxin because maize tolerant to HC-toxin is more sensitive to chlamydocin and Cyl-2.  相似文献   
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This paper describes multi-view modeling and data model transformation for the modeling. We have proposed a reference model of CAD system generation, which can be applied to various domain-specific languages. However, the current CAD system generation cannot integrate data of multiple domains. Generally each domain has its own view of products. For example, in the domain of architectural structure, designers extract the necessary data from the data in architecture design. Domain experts translate one view into another view beyond domains using their own brains. The multi-view modeling is a way to integrate product data of multiple domains, and make it possible to translate views among various domains by computers.  相似文献   
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H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-alpha2,6-galactose (SAalpha2,6Gal), whereas the latter prefer those ending in SAalpha2,3Gal (refs 3-6). A conversion from SAalpha2,3Gal to SAalpha2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.  相似文献   
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