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   2496篇
  免费   171篇
  2024年   3篇
  2023年   17篇
  2022年   31篇
  2021年   85篇
  2020年   50篇
  2019年   57篇
  2018年   78篇
  2017年   48篇
  2016年   104篇
  2015年   159篇
  2014年   207篇
  2013年   212篇
  2012年   247篇
  2011年   249篇
  2010年   152篇
  2009年   123篇
  2008年   159篇
  2007年   146篇
  2006年   110篇
  2005年   109篇
  2004年   85篇
  2003年   81篇
  2002年   69篇
  2001年   13篇
  2000年   5篇
  1999年   14篇
  1998年   14篇
  1997年   8篇
  1996年   4篇
  1995年   6篇
  1994年   4篇
  1993年   4篇
  1992年   4篇
  1991年   3篇
  1990年   1篇
  1988年   1篇
  1987年   1篇
  1984年   1篇
  1983年   1篇
  1981年   2篇
排序方式: 共有2667条查询结果,搜索用时 582 毫秒
991.
992.
Worker and queen bees are genetically indistinguishable. However, queen bees are fertile, larger and have a longer lifespan than their female worker counterparts. Differential feeding of larvae with royal jelly controls this caste switching. There is emerging evidence that the queen-bee phenotype is driven by epigenetic mechanisms. In this study, we show that royal jelly--the secretion produced by the hypopharyngeal and mandibular glands of worker bees--has histone deacetylase inhibitor (HDACi) activity. A fatty acid, (E)-10-hydroxy-2-decenoic acid (10HDA), which accounts for up to 5% of royal jelly, harbours this HDACi activity. Furthermore, 10HDA can reactivate the expression of epigenetically silenced genes in mammalian cells. Thus, the epigenetic regulation of queen-bee development is probably driven, in part, by HDACi activity in royal jelly.  相似文献   
993.
With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.  相似文献   
994.
Protein phosphorylation constitutes a major type of post-translational modification that mobilizes a high number of genes, especially in plants, is involved in many crucial cell functions and largely participates to the complexity of the proteomes. For several biological and technical reasons, the characterization of phosphorylation sites requires complex procedures. In this review, the different approaches presently available to select phosphoproteins and phosphopeptides are described. A special emphasis is then given to the numerous strategies that have emerged for the analysis of phosphorylation sites by various techniques of mass spectrometry. Finally, the few attempts proposed for the quantification of phosphorylation events are presented. In another part, the results of the efforts made in the plant area to analyze the phosphoproteome are compared to those in other biological systems. These overviews are put together to delineate, according to the objectives pursued, the different strategies possible and the corresponding challenges.  相似文献   
995.
The Cerrado, the savanna biome in central Brazil, mostly comprised of woodland savanna, is experiencing intense and fast land use changes. To understand the changes in Cerrado carbon stocks, we present an overview of biomass distribution in different Cerrado vegetation types (i.e., grasslands, shrublands and forestlands). We surveyed 26 studies including 170 Cerrado sites. The grasslands presented mean total biomass of 24 Mg/ha, with 70 percent allocated in the belowground portion. In shrublands, the mean total biomass was 58 Mg/ha being 58 percent in the belowground portion. Finally, in forestlands the mean total biomass was 98 Mg/ha with 18 percent as belowground biomass. The surveyed studies presented 12 allometric equations for biomass estimate, most involving both diameter and height. Data on wood density for Cerrado shrubs and trees are not abundant and the average value was 0.66 g/cm3, similar to that found in the central portion of the Amazon Forest. We also examined the relationship between total precipitation and dry‐season intensity with biomass variation in the Cerrado shrubland using data from tropical rainfall measurement mission (TRMM) for the period 2000–2010. Dry‐season precipitation amount in cerrado areas in severe drought regions explained 29 percent of the variation in aboveground woody biomass. This finding is important in the face of the predictions of longer and more severe dry seasons in the region due to climate change.  相似文献   
996.
997.
SUMMARY Morphological integration corresponds to interdependency between characters that can arise from several causes. Proximal causes of integration include that different phenotypic features may share common genetic sets and/or interact during their development. Ultimate causes may be the prolonged effect of selection favoring integration of functionally interacting characters, achieved by the molding of these proximal causes. Strong and direct interactions among successive teeth of a molar row are predicted by genetic and developmental evidences. Functional constraints related to occlusion, however, should have selected more strongly for a morphological integration of occluding teeth and a corresponding evolution of the underlying developmental and genetic pathways. To investigate how these predictions match the patterns of phenotypic integration, we studied the co‐variation among the six molars of the murine molar row, focusing on two populations of house mice (Mus musculus domesticus) and wood mice (Apodemus sylvaticus). The size and shape of the three upper and lower molars were quantified and compared. Our results evidenced similar patterns in both species, size being more integrated than shape among all the teeth, and both size and shape co‐varying strongly between adjacent teeth, but also between occluding teeth. Strong co‐variation within each molar row is in agreement with developmental models showing a cascade influence of the first molar on the subsequent molars. In contrast, the strong co‐variation between molars of the occluding tooth rows confirms that functional constraints molded patterns of integration and probably the underlying developmental pathways despite the low level of direct developmental interactions occurring among molar rows. These patterns of co‐variation are furthermore conserved between the house mouse and the wood mouse that diverged >10 Ma, suggesting that they may constitute long‐running constraints to the diversification of the murine rodent dentition.  相似文献   
998.
999.
Clathrin depletion by ribonucleic acid interference (RNAi) impairs mitotic spindle stability and cytokinesis. Depletion of several clathrin-associated proteins affects centrosome integrity, suggesting a further cell cycle function for clathrin. In this paper, we report that RNAi depletion of CHC17 (clathrin heavy chain 17) clathrin, but not the CHC22 clathrin isoform, induced centrosome amplification and multipolar spindles. To stage clathrin function within the cell cycle, a cell line expressing SNAP-tagged clathrin light chains was generated. Acute clathrin inactivation by chemical dimerization of the SNAP-tag during S phase caused reduction of both clathrin and ch-TOG (colonic, hepatic tumor overexpressed gene) at metaphase centrosomes, which became fragmented. This was phenocopied by treatment with Aurora A kinase inhibitor, suggesting a centrosomal role for the Aurora A-dependent complex of clathrin, ch-TOG, and TACC3 (transforming acidic coiled-coil protein 3). Clathrin inactivation in S phase also reduced total cellular levels of ch-TOG by metaphase. Live-cell imaging showed dynamic clathrin recruitment during centrosome maturation. Therefore, we propose that clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin-ch-TOG-TACC3 complex.  相似文献   
1000.
Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC–MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.  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