全文获取类型
收费全文 | 2146篇 |
免费 | 193篇 |
出版年
2021年 | 29篇 |
2020年 | 13篇 |
2019年 | 28篇 |
2018年 | 40篇 |
2017年 | 33篇 |
2016年 | 60篇 |
2015年 | 88篇 |
2014年 | 81篇 |
2013年 | 128篇 |
2012年 | 152篇 |
2011年 | 153篇 |
2010年 | 81篇 |
2009年 | 78篇 |
2008年 | 116篇 |
2007年 | 120篇 |
2006年 | 108篇 |
2005年 | 84篇 |
2004年 | 93篇 |
2003年 | 105篇 |
2002年 | 87篇 |
2001年 | 46篇 |
2000年 | 31篇 |
1999年 | 29篇 |
1998年 | 25篇 |
1997年 | 26篇 |
1996年 | 16篇 |
1995年 | 14篇 |
1994年 | 21篇 |
1993年 | 10篇 |
1992年 | 13篇 |
1991年 | 24篇 |
1990年 | 15篇 |
1989年 | 19篇 |
1988年 | 17篇 |
1987年 | 18篇 |
1986年 | 26篇 |
1985年 | 29篇 |
1984年 | 16篇 |
1983年 | 17篇 |
1982年 | 12篇 |
1981年 | 15篇 |
1980年 | 20篇 |
1979年 | 24篇 |
1978年 | 24篇 |
1977年 | 19篇 |
1976年 | 18篇 |
1974年 | 15篇 |
1973年 | 19篇 |
1972年 | 8篇 |
1967年 | 7篇 |
排序方式: 共有2339条查询结果,搜索用时 171 毫秒
91.
Marie‐Pierre Ledru Vincent Montade Grégoire Blanchard Christelle Hély 《Biotropica》2016,48(2):159-169
The aim of this study is to represent simultaneously changes in the spatial distribution of the Atlantic forest during the last 17,000 years. To characterize such changes, here we focused on three different forest physiognomies, evergreen, semi‐deciduous, and Araucaria, and we provide a list of indicator taxa for each class retrieved from the original published datasets. A review of the published fossil pollen records allowed us to classify regional behaviors in three main areas of distribution, north of 15°S, between 15° and 23°S and south of 23°S latitude that correspond to three climatic geographical barriers. Statistical probability density function method was used to illustrate changes in forest physiognomies throughout the three distribution areas. We show that the three modern barriers also functioned through the past. Asynchronous patterns of forest physiognomies are linked to an antiphasing pattern of monsoon precipitation between the northern and central area, whereas in the southern area, it is linked to the frequency and intensity of the polar advection in the subtropics. Our results attest to strong climate forcing on forest distribution between the late glacial and the interglacial period. They call into question the common reference to the last glacial maximum as a major (and sometimes as the only) driver of forest‐related vicariance and genetic diversity patterns, but suggest that instead, orbital cycles were the main drivers of the successive expansion/contraction of the Atlantic forest throughout the Quaternary. 相似文献
92.
93.
94.
Steven Rudeck Christelle Etard Muzamil M. Khan Wolfgang Rottbauer Rüdiger Rudolf Uwe Strhle Steffen Just 《Genesis (New York, N.Y. : 2000)》2016,54(8):431-438
Summary: Gene therapeutic approaches to cure genetic diseases require tools to express the rescuing gene exclusively within the affected tissues. Viruses are often chosen as gene transfer vehicles but they have limited capacity for genetic information to be carried and transduced. In addition, to avoid off‐target effects the therapeutic gene should be driven by a tissue‐specific promoter in order to ensure expression in the target organs, tissues, or cell populations. The larger the promoter, the less space will be left for the respective gene. Thus, there is a need for small but tissue‐specific promoters. Here, we describe a compact unc45b promoter fragment of 195 bp that retains the ability to drive gene expression exclusively in skeletal and cardiac muscle in zebrafish and mouse. Remarkably, the described unc45b promoter fragment not only drives muscle‐specific expression but presents heat‐shock inducibility, allowing a temporal and spatial quantity control of (trans)gene expression. Here, we demonstrate that the transgenic expression of the smyd1b gene driven by the unc45b promoter fragment is able to rescue the embryonically lethal heart and skeletal muscle defects in smyd1b‐deficient flatline mutant zebrafish. Our findings demonstrate that the described muscle‐specific unc45b promoter fragment might be a valuable tool for the development of genetic therapies in patients suffering from myopathies. genesis 54:431–438, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc. 相似文献
95.
Thibault Teissier Valentine Quersin Viviane Gnemmi Mait Daroux Mike Howsam Florian Delguste Ccile Lemoine Chantal Fradin Ann‐Marie Schmidt Christelle Cauffiez Thierry Brousseau Franois Glowacki Frdric J. Tessier Eric Boulanger Marie Frimat 《Aging cell》2019,18(2)
Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE?/? C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/gfood) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE?/? mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE?/? mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE?/? mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE?/? mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE?/? mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging. 相似文献
96.
Gaëlle Lentini David J. Dubois Bohumil Maco Dominique Soldati‐Favre Karine Frnal 《Traffic (Copenhagen, Denmark)》2019,20(8):583-600
To efficiently enter host cells, apicomplexan parasites such as Toxoplasma gondii rely on an apical complex composed of tubulin‐based structures as well as two sets of secretory organelles named micronemes and rhoptries. The trafficking and docking of these organelles to the apical pole of the parasite is crucial for the discharge of their contents. Here, we describe two proteins typically associated with microtubules, Centrin 2 (CEN2) and Dynein Light Chain 8a (DLC8a), that are required for efficient host cell invasion. CEN2 localizes to four different compartments, and remarkably, conditional depletion of the protein occurs in stepwise manner, sequentially depleting the protein pools from each location. This phenomenon allowed us to discern the essential function of the apical pool of CEN2 for microneme secretion, motility, invasion and egress. DLC8a localizes to the conoid, and its depletion also perturbs microneme exocytosis in addition to the apical docking of the rhoptry organelles, causing a severe defect in host cell invasion. Phenotypic characterization of CEN2 and DLC8a indicates that while both proteins participate in microneme secretion, they likely act at different steps along the cascade of events leading to organelle exocytosis. 相似文献
97.
PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress
98.
Interleukin-13 interferes with CFTR and AQP5 expression and localization during human airway epithelial cell differentiation 总被引:1,自引:0,他引:1
Skowron-zwarg M Boland S Caruso N Coraux C Marano F Tournier F 《Experimental cell research》2007,313(12):2695-2702
Interleukin-13 (IL-13) is a central regulator of Th2-dominated respiratory disorders such as asthma. Lesions of the airway epithelial barrier frequently observed in chronic respiratory inflammatory diseases are repaired through proliferation, migration and differentiation of epithelial cells. Our work is focused on the effects of IL-13 in human cellular models of airway epithelial cell regeneration. We have previously shown that IL-13 altered epithelial cell polarity during mucociliary differentiation of human nasal epithelial cells. In particular, the cytokine inhibited ezrin expression and interfered with its apical localization during epithelial cell differentiation in vitro. Here we show that CFTR expression is enhanced in the presence of the cytokine, that two additional CFTR protein isoforms are expressed in IL-13-treated cells and that part of the protein is retained within the endoplasmic reticulum. We further show that aquaporin 5 expression, a water channel localized within the apical membrane of epithelial cells, is completely abolished in the presence of the cytokine. These results show that IL-13 interferes with ion and water channel expression and localization during epithelial regeneration and may thereby influence mucus composition and hydration. 相似文献
99.
Devader C Drew CM Geach TJ Tabler J Townsend-Nicholson A Dale L 《FEBS letters》2007,581(27):5332-5336
We describe a Xenopus P2Y receptor that shares only weak homology with members of the mammalian P2Y family, being most similar to human P2Y(11). When activated by nucleotide analogs, it stimulates both calcium and cAMP mobilization pathways, a feature unique, among mammalian P2Y receptors, to P2Y(11). Activity can be blocked by compounds known to act as antagonists of mammalian P2Y(11). Genomic synteny between Xenopus and mammals suggests that the novel gene is a true ortholog of P2Y(11). Xenopus P2Y(11) is transcribed during embryonic development, beginning at gastrulation, and is enriched in the developing nervous system. 相似文献
100.