首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   93篇
  免费   5篇
  国内免费   4篇
  2022年   2篇
  2021年   4篇
  2020年   4篇
  2019年   1篇
  2018年   2篇
  2017年   2篇
  2016年   4篇
  2015年   3篇
  2014年   2篇
  2013年   5篇
  2012年   6篇
  2011年   3篇
  2010年   3篇
  2009年   4篇
  2008年   2篇
  2007年   5篇
  2006年   4篇
  2004年   7篇
  2003年   3篇
  2001年   3篇
  2000年   3篇
  1998年   3篇
  1997年   2篇
  1996年   2篇
  1995年   2篇
  1993年   2篇
  1991年   1篇
  1990年   1篇
  1989年   1篇
  1982年   1篇
  1979年   1篇
  1978年   1篇
  1976年   1篇
  1972年   1篇
  1971年   1篇
  1955年   1篇
  1954年   4篇
  1950年   1篇
  1934年   1篇
  1916年   1篇
  1906年   1篇
  1905年   1篇
排序方式: 共有102条查询结果,搜索用时 31 毫秒
31.
The sialomucin endolyn is implicated in adhesion, migration, and differentiation of various cell types. Along rat kidney tubules, endolyn is variously localized to the apical surface and endosomal/lysosomal compartments. Apical delivery of newly synthesized rat endolyn predominates over direct lysosomal delivery in polarized Madin-Darby canine kidney cells. Apical sorting depends on terminal processing of a subset of lumenal N-glycans. Here we dissect the requirements of N-glycan processing for apical targeting and investigate the underlying mechanism. Modulation of glycan branching and subsequent polylactosamine elongation by knockdown of N-acetylglucosaminyltransferase III or V had no effect on apical delivery of endolyn. In contrast, combined but not individual knockdown of sialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are responsible for addition of α2,3- and α2,6-linked sialic acids on N-glycans, dramatically decreased endolyn surface polarity. Endolyn synthesized in the presence of kifunensine, which blocks terminal N-glycan processing, reduced its interaction with several recombinant canine galectins, and knockdown of galectin-9 (but not galectin-3, -4, or -8) selectively disrupted endolyn polarity. Our data suggest that sialylation enables recognition of endolyn by galectin-9 to mediate efficient apical sorting. They raise the intriguing possibility that changes in glycosyltransferase expression patterns and/or galectin-9 distribution may acutely modulate endolyn trafficking in the kidney.  相似文献   
32.
33.
34.
35.
We previously demonstrated that, in contrast to the hydrolysis of ATP, the hydrolysis of GTP by canine cardiac sarcoplasmic reticulum is not sensitive to calcium. Based on a variety of qualitative and quantitative considerations (cf. Tate, C. A., Bick, R. J., Chu, A., Van Winkle, W. B., and Entman, M. L. (1985) J. Biol. Chem. 260, 9618-9623), we suggested that the hydrolysis of ATP and GTP appears to be effected by the same enzyme. In the present paper, we examined the sensitivity of both enzymatic activities to low concentrations of detergent. With nonsolubilizing concentrations of the nonionic detergent, octaethylene glycol monododecyl ether, the hydrolysis of GTP was rendered partially calcium-sensitive resulting from a slightly increased total (Ca2+ + Mg2+)-GTPase activity and a markedly inhibited calcium-independent (Mg2+-dependent) GTPase activity. Calcium-dependent ATPase activity was increased with octaethylene glycol monododecyl ether, mimicking the effect of the ionophore, A23187. Calcium-dependent ATPase activity and detergent-induced calcium-dependent GTPase activity were similar in (a) calcium sensitivity, (b) sensitivity to mersalyl, and (c) pressure inactivation through dilution and centrifugation, all of which differed from the untreated calcium-independent GTPase activity. Calcium-dependent ATPase activity differed from calcium-dependent GTPase activity with (a) a higher nucleotide affinity, (b) a lower vanadate sensitivity, and (c) a calcium sensitivity for phosphoenzyme formation. Thus, the detergent-induced perturbation of the GTPase resulted in an enzyme with many characteristics qualitatively and quantitatively similar to the calcium ATPase.  相似文献   
36.
37.
38.
A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical–experimental framework for disclosing the presence of such adaptation‐speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation–accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic‐adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data‐driven individual‐based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation‐speeding mechanisms in general.  相似文献   
39.
Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources. The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples. Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k- ¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data. Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing algorithms.  相似文献   
40.
The sorting signals that direct proteins to the apical surface of polarized epithelial cells are complex and can include posttranslational modifications, such as N- and O-linked glycosylation. Efficient apical sorting of the neurotrophin receptor p75 is dependent on its O-glycosylated membrane proximal stalk, but how this domain mediates targeting is unknown. Protein oligomerization or clustering has been suggested as a common step in the segregation of all apical proteins. Like many apical proteins, p75 forms dimers, and we hypothesized that formation of higher-order clusters mediated by p75 dimerization and interactions of the stalk facilitate its apical sorting. Using fluorescence fluctuation techniques (photon-counting histogram and number and brightness analyses) to study p75 oligomerization status in vivo, we found that wild-type p75–green fluorescent protein forms clusters in the trans-Golgi network (TGN) but not at the plasma membrane. Disruption of either the dimerization motif or the stalk domain impaired both clustering and polarized delivery. Manipulation of O-glycan processing or depletion of multiple galectins expressed in Madin-Darby canine kidney cells had no effect on p75 sorting, suggesting that the stalk domain functions as a structural prop to position other determinants in the lumenal domain of p75 for oligomerization. Additionally, a p75 mutant with intact dimerization and stalk motifs but with a dominant basolateral sorting determinant (Δ250 mutant) did not form oligomers, consistent with a requirement for clustering in apical sorting. Artificially enhancing dimerization restored clustering to the Δ250 mutant but was insufficient to reroute this mutant to the apical surface. Together these studies demonstrate that clustering in the TGN is required for normal biosynthetic apical sorting of p75 but is not by itself sufficient to reroute a protein to the apical surface in the presence of a strong basolateral sorting determinant. Our studies shed new light on the hierarchy of polarized sorting signals and on the mechanisms by which newly synthesized proteins are segregated in the TGN for eventual apical delivery.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号