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   1246篇
  免费   88篇
  2022年   11篇
  2021年   22篇
  2020年   8篇
  2019年   11篇
  2018年   31篇
  2017年   12篇
  2016年   20篇
  2015年   44篇
  2014年   61篇
  2013年   57篇
  2012年   92篇
  2011年   93篇
  2010年   56篇
  2009年   54篇
  2008年   66篇
  2007年   87篇
  2006年   73篇
  2005年   68篇
  2004年   49篇
  2003年   49篇
  2002年   81篇
  2001年   10篇
  2000年   11篇
  1999年   6篇
  1998年   24篇
  1997年   17篇
  1996年   10篇
  1995年   9篇
  1994年   7篇
  1993年   11篇
  1992年   14篇
  1991年   13篇
  1990年   6篇
  1989年   11篇
  1988年   7篇
  1987年   9篇
  1986年   7篇
  1985年   8篇
  1984年   11篇
  1982年   8篇
  1981年   7篇
  1980年   7篇
  1979年   5篇
  1977年   5篇
  1976年   11篇
  1974年   5篇
  1973年   4篇
  1972年   5篇
  1971年   8篇
  1969年   5篇
排序方式: 共有1334条查询结果,搜索用时 500 毫秒
181.
Temperate grasslands have suffered disproportionally from conversion to cropland, degradation and fragmentation. A large proportion of the world’s remaining near-natural grassland is situated in Kazakhstan. We aimed to assess current and emerging threats to steppe and semi-desert biodiversity in Kazakhstan and evaluate conservation research priorities. We conducted a horizon-scanning exercise among conservationists from academia and practice. We first compiled a list of 45 potential threats. These were then ranked by the survey participants according to their perceived severity, the need for research on them, and their novelty. The highest-ranked threats were related to changes in land use (leading to habitat loss and deterioration), direct persecution of wildlife, and rapid infrastructure development due to economic and population growth. Research needs were identified largely in the same areas, and the mean scores of threat severity and research need were highly correlated. Novel threats comprised habitat loss by photovoltaic and wind power stations, climate change and changes in agriculture such as the introduction of biofuels. However, novelty was not correlated with threat severity or research priority, suggesting that the most severe threats are the established ones. Important goals towards more effective steppe and semi-desert conservation in Kazakhstan include more cross-sector collaboration (e.g. by involving stakeholders in conservation and agriculture), greater allocation of funds to under-staffed areas (e.g. protected area management), better representativeness and complementarity in the protected area system and enhanced data collection for wildlife monitoring and threat assessments (including the use of citizen-science databases).  相似文献   
182.
183.
184.
Human immunodeficiency virus (HIV) infection leads to a decline of CD4+ T-cells in blood. Because blood represents only a small proportion of the total lymphocyte pool, it is important to investigate other lymphoid organs. So far, only relative proportions of lymphocyte subsets in single peripheral lymph node (LN) regions of HIV-infected patients and simian immunodeficiency virus (SIV)-infected macaques have been documented. We have therefore quantified the absolute numbers of lymphocyte subsets in blood and six different LN regions of 10 uninfected and 26 SIV-infected macaques. In addition, we have determined the expression of markers of activation and differentiation. Already, in uninfected monkeys, there were significant differences in the cellular composition of different LN regions. Infection with SIV resulted in drastic changes in the proportion as well as absolute numbers of different lymphocyte subsets. Moreover, the relative contribution of the single LN regions to the total lymphocyte pool was also altered.  相似文献   
185.
14-3-3 Proteins are thought to function as adapters in signaling complexes [1,2], thereby participating in cellular processes including vesicle trafficking and exocytosis [3,4]. To delineate further the function of 14-3-3 proteins during vesicle trafficking, we generated dominant-negative alleles of the two 14-3-3 homologues, Bmh1p and Bmh2p, in budding yeast and analyzed their phenotype in respect to exocytosis. Cells overexpressing the carboxy-terminal region of Bmh2p failed to polarize vesicular transport although bulk exocytosis remained unaffected and showed a disrupted actin cytoskeleton. Our data suggest that 14-3-3 proteins may act primarily on the actin cytoskeleton to regulate vesicle targeting.  相似文献   
186.
Aminopeptidase N (APN)/CD13 is a transmembrane ectoenzyme expressed on a wide variety of cells. With respect to haematopoietic cells, APN/CD13 has been considered specific for the myeloid lineage, because granulocytes and monocytes/macrophages, but not lymphocytes of peripheral blood, show a surface expression of CD13 antigen. However, we could recently show that cell‐cell contact of lymphocytes with endothelial cells, monocytes, and fibroblast‐like synoviocytes (SFCs) results in an increase of steady‐state APN/CD13 mRNA and a rapid expression of cell‐surface protein on the lymphocytes. In this study using the Dual‐Luciferase reporter assay, we demonstrate that interaction of the T‐cell line Jurkat with SFCs results in a higher activity of the APN/CD13 myeloid promoter in T cells. An enhancer located between the myeloid and epithelial APN/CD13 promoter increases the response of the promoter to the cell‐cell contact‐induced expression of APN/CD13 in lymphocytes. Adhesion of lymphocytes to extracellular matrix did not result in increased promoter activity. The lymphocytic promoter response induced by direct cell‐cell contact with SFCs is not affected by mutations of a proximal promoter element (nucleotides −48 to −35), which has a possible functional role in the basal APN/CD13 gene expression in lymphocytes. Upregulated peptidase‐promoter activity via cell‐cell contact shown in this study for the first time is discussed as a general mechanism in peptidase induction. J. Cell. Biochem. 80:115–123, 2000. © 2000 Wiley‐Liss, Inc.  相似文献   
187.
Lateral plate and uropod glands are composed of a binucleated gland cell, a ramified intermediate cell, and an elongated duct cell. The gland cell is divided into several lobes and forms numerous short processes in its periphery. The cytoplasm contains many secretory granules. The granules release their content into the intercellular collecting ducts between the gland cell and the branched extensions of the intermediate cell. The collecting ducts merge into a funnel-shaped space surrounded by the intermediate cell. The duct cell is lined by a cuticular intima and contains long striated bundles of fibrils. The duct cell consists of two different regions. The proximal region is characterized by microvilli on the luminal side and contains many organelles. In the distal region microvilli are lacking and organelles are scarce. Structurally, the uropod and lateral plate glands differ in the number of components within the granules. This is in accordance with the differences in the characteristics of the secretory products of the two gland types. The morphology of the glands, particularly the peripheral position of the collecting system, is unique among exocrine glands of arthropods. J. Morphol. 233:183–193, 1997 © 1997 Wiley-Liss, Inc.  相似文献   
188.
Vertebrate gut microbiota (GM) is comprised of a taxonomically diverse consortium of symbiotic and commensal microorganisms that have a pronounced effect on host physiology, immune system function and health status. Despite much research on interactions between hosts and their GM, the factors affecting inter‐ and intraspecific GM variation in wild populations are still poorly known. We analysed data on faecal microbiota composition in 51 passerine species (319 individuals) using Illumina MiSeq sequencing of bacterial 16S rRNA (V3–V4 variable region). Despite pronounced interindividual variation, GM composition exhibited significant differences at the interspecific level, accounting for approximately 20%–30% of total GM variation. We also observed a significant correlation between GM composition divergence and host's phylogenetic divergence, with strength of correlation higher than that of GM vs. ecological or life history traits and geographic variation. The effect of host's phylogeny on GM composition was significant, even after statistical control for these confounding factors. Hence, our data do not support codiversification of GM and passerine phylogeny solely as a by‐product of their ecological divergence. Furthermore, our findings do not support that GM vs. host's phylogeny codiversification is driven primarily through trans‐generational GM transfer as the GM vs. phylogeny correlation does not increase with higher sequence similarity used when delimiting operational taxonomic units. Instead, we hypothesize that the GM vs. phylogeny correlation may arise as a consequence of interspecific divergence of genes that directly or indirectly modulate composition of GM.  相似文献   
189.

Background

Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer’s disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used. However, quality control of these antibodies is lacking and their specificity for particular modifications is often unclear.

Methods

In this study, we first designed an online tool called ‘TauPTM’, which enables the visualization of PTMs and their interactions on human tau. Using TauPTM, we next searched for commercially available antibodies against tau PTMs and characterized their specificity by peptide array, immunoblotting, electrochemiluminescence ELISA and immunofluorescence technologies.

Results

We demonstrate that commercially available antibodies can show a significant lack of specificity, and PTM-specific antibodies in particular often recognize non-modified versions of the protein. In addition, detection may be hindered by other PTMs in close vicinity, complicating the interpretation of results. Finally, we compiled a panel of specific antibodies and show that they are useful to detect PTM-modified endogenous tau in hiPSC-derived neurons and mouse brains.

Conclusion

This study has created a platform to reliably and robustly detect changes in localization and abundance of post-translationally modified tau in health and disease. A web-based version of TauPTM is fully available at http://www.tauptm.org.
  相似文献   
190.
Different classes of endosomes exhibit a characteristic intracellular steady-state distribution governed by interactions with the cytoskeleton. Late endosomes, organelles of the degradative lysosomal route, seem to require associated actin filaments for proper localization and function. We show here that the F-actin and phospholipid binding protein annexin A8 is associated specifically with late endosomes. Altering intracellular annexin A8 levels drastically affected the morphology and intracellular distribution of late endosomes. Trafficking through the degradative pathway was delayed in the absence of annexin A8, resulting in attenuated ligand-induced degradation of the epidermal growth factor receptor and prolonged epidermal growth factor-induced activation of mitogen-activated protein kinase. Depletion of annexin A8 reduced the association of late endosomal membranes with actin filaments. These results indicate that the defective cargo transport through the late endocytic pathway and the imbalanced signaling of activated receptors observed in the absence of annexin A8 results from the disturbed association of late endosomal membranes with the actin network, resulting in impaired actin-based late endosome motility.  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