全文获取类型
收费全文 | 6712篇 |
免费 | 601篇 |
国内免费 | 3篇 |
专业分类
7316篇 |
出版年
2023年 | 37篇 |
2022年 | 74篇 |
2021年 | 159篇 |
2020年 | 72篇 |
2019年 | 123篇 |
2018年 | 139篇 |
2017年 | 113篇 |
2016年 | 197篇 |
2015年 | 341篇 |
2014年 | 437篇 |
2013年 | 534篇 |
2012年 | 578篇 |
2011年 | 572篇 |
2010年 | 365篇 |
2009年 | 341篇 |
2008年 | 444篇 |
2007年 | 428篇 |
2006年 | 416篇 |
2005年 | 386篇 |
2004年 | 341篇 |
2003年 | 317篇 |
2002年 | 305篇 |
2001年 | 45篇 |
2000年 | 50篇 |
1999年 | 71篇 |
1998年 | 63篇 |
1997年 | 42篇 |
1996年 | 35篇 |
1995年 | 36篇 |
1994年 | 30篇 |
1993年 | 28篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 9篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1983年 | 12篇 |
1981年 | 3篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有7316条查询结果,搜索用时 0 毫秒
61.
Aline Frville Bndicte Gnangnon Annie Z. Tremp Caroline De Witte Katia Cailliau Alain Martoriati El Moukthar Aliouat Priyanka Fernandes Cerina Chhuon Olivier Silvie Sabrina Marion Ida Chiara Guerrera Johannes T. Dessens Christine Pierrot Jamal Khalife 《Open biology》2022,12(8)
Protein phosphatase 1 (PP1) is a key enzyme for Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the Plasmodium berghei leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of Plasmodium PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of Plasmodium oocyst development through its interaction with PbLRR1. 相似文献
62.
63.
Y‐craniosynostosis by premature fusion of the metopic and coronal sutures: A new nosological entity or a variety of Saethre‐Chotzen syndrome? 下载免费PDF全文
64.
Body size can influence an organism's microevolutionary fitness either via ecological factors (ecological selection) or changes in reproductive output (sexual or fecundity selection). Published studies on sexual dimorphism in reptiles have generally focussed on sexual-selective forces on males, under the implicit assumption that the intensity of fecundity selection in females (and hence, overall selection on female body size) is likely to be relatively consistent among lineages. In this paper, we explore the degree to which larger body size enhances ecological attributes (e.g., food intake, growth, survival) and reproductive output (reproductive frequency, litter size, offspring size, offspring viability) in free-ranging female aspic vipers, Vipera aspis . The less-than-annual reproductive frequency of these animals allows us to make a direct comparison between females in years during which they concentrate on "ecological" challenges (especially building energy reserves) versus reproductive challenges (producing a litter). Because female snakes have limited abdominal space to hold the clutch (litter), we expect that fecundity should depend on body size. However, our data show that larger body size had a more consistent effect on ecological attributes (such as feeding rates and "costs of reproduction") than on reproductive output per se. Indeed, total reproductive output was maximised at intermediate body sizes. These results suggest that variation in female body size among and within species (and hence, in the degree of sexual dimorphism) may be driven by the ecological as well as reproductive consequences of body size variation in both sexes. 相似文献
65.
Sarah Rouhana Charlotte Farah Jerome Roy Amanda Finan Glaucy Rodrigues de Araujo Patrice Bideaux Valérie Scheuermann Youakim Saliba Cyril Reboul Olivier Cazorla Franck Aimond Sylvain Richard Jérôme Thireau Nassim Fares 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):230-242
Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. We investigated the cellular phenotype and Ca2+ handling in hearts recapitulating HFpEF criteria. HFpEF was induced in a portion of male Wistar rats four weeks after abdominal aortic banding. These animals had nearly normal ejection fraction and presented elevated blood pressure, lung congestion, concentric hypertrophy, increased LV mass, wall stiffness, impaired active relaxation and passive filling of the left ventricle, enlarged left atrium, and cardiomyocyte hypertrophy. Left ventricular cell contraction was stronger and the Ca2+ transient larger. Ca2+ cycling was modified with a RyR2 mediated Ca2+ leak from the sarcoplasmic reticulum and impaired Ca2+ extrusion through the Sodium/Calcium exchanger (NCX), which promoted an increase in diastolic Ca2+. The Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a) and NCX protein levels were unchanged. The phospholamban (PLN) to SERCA2a ratio was augmented in favor of an inhibitory effect on the SERCA2a activity. Conversely, PLN phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLN-Thr17), which promotes SERCA2A activity, was increased as well, suggesting an adaptive compensation of Ca2+ cycling. Altogether our findings show that cardiac remodeling in hearts with a HFpEF status differs from that known for heart failure with reduced ejection fraction. These data also underscore the interdependence between systolic and diastolic “adaptations” of Ca2+ cycling with complex compensative interactions between Ca2+ handling partner and regulatory proteins. 相似文献
66.
AIMS: The objective of the study was to assess the pharmacodynamic equivalence of LHRH analogue triptorelin 3-month and 28-day SR formulations. METHODS: Patients with documented locally advanced or metastatic prostate cancer were randomized to receive one injection of the 3-month formulation (n = 63) or three injections at 28-day intervals of the 28-day formulation (n = 68). Group-chemical castration rates defined as the percentage of patients reaching a testosterone plasma level =0.5 ng/ml were compared at D84 (i.e., 3 x 28 days). Testosterone, LH and triptorelin plasma profiles, and change from baseline in plasma PSA were assessed over 3 months (from baseline to D91). RESULTS: Chemical castration rates were 98 and 96% in the 3-month and 28-day formulation groups, respectively, with confidence interval (two-sided 94.2% CI) of [-8.1%; 9.6%]. Median times to reach chemical castration were 18.8 and 18.5 days (p = 0.86, log rank), respectively. Ratios for mean peak plasma levels and AUC(91) of the two formulations for both testosterone and LH fell within the [0.80; 1.25] equivalence interval. Mean PSA decreases from baseline at D91 were 91.0 and 91.7%, respectively (p = 0.73). CONCLUSION: Treatments with the two triptorelin formulations over 3 months are pharmacologically equivalent. 相似文献
67.
Antje Motzek Jelena Kne?evi? Olivier J. Switzeny Alexis Cooper Ivo Bari? Robert Beluzi? Kevin A. Strauss Erik G. Puffenberger S. Harvey Mudd Oliver Vugrek Ulrich Zechner 《PloS one》2016,11(3)
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors. In this study, we set out to more specifically characterize DNA methylation changes in blood samples from patients with AHCY deficiency. Global DNA methylation was increased in two of three analysed patients. In addition, we analysed the DNA methylation levels at differentially methylated regions (DMRs) of six imprinted genes (MEST, SNRPN, LIT1, H19, GTL2 and PEG3) as well as Alu and LINE1 repetitive elements in seven patients. Three patients showed a hypermethylation in up to five imprinted gene DMRs. Abnormal methylation in Alu and LINE1 repetitive elements was not observed. We conclude that DNA hypermethylation seems to be a frequent but not a constant feature associated with AHCY deficiency that affects different genomic regions to different degrees. Thus AHCY deficiency may represent an ideal model disease for studying the molecular origins and biological consequences of DNA hypermethylation due to impaired cellular methylation status. 相似文献
68.
69.
Olivier Maurin Artemis Anest Sidonie Bellot Edward Biffin Grace Brewer Tristan Charles-Dominique Robyn S. Cowan Steven Dodsworth Niroshini Epitawalage Berta Gallego Augusto Giaretta Renato Goldenberg Deise J.P. Gonçalves Shirley Graham Peter Hoch Fiorella Mazine Yee Wen Low Catherine McGinnie Fabián A. Michelangeli Sarah Morris Darin S. Penneys Oscar Alejandro Pérez Escobar Yohan Pillon Lisa Pokorny Gustavo Shimizu Vanessa G. Staggemeier Andrew H. Thornhill Kyle W. Tomlinson Ian M. Turner Thais Vasconcelos Peter G. Wilson Alexandre R. Zuntini William J. Baker Félix Forest Eve Lucas 《American journal of botany》2021,108(7):1087-1111
70.