全文获取类型
收费全文 | 3130篇 |
免费 | 278篇 |
国内免费 | 1篇 |
专业分类
3409篇 |
出版年
2023年 | 35篇 |
2022年 | 53篇 |
2021年 | 119篇 |
2020年 | 69篇 |
2019年 | 79篇 |
2018年 | 94篇 |
2017年 | 86篇 |
2016年 | 138篇 |
2015年 | 174篇 |
2014年 | 196篇 |
2013年 | 250篇 |
2012年 | 322篇 |
2011年 | 304篇 |
2010年 | 149篇 |
2009年 | 138篇 |
2008年 | 185篇 |
2007年 | 190篇 |
2006年 | 163篇 |
2005年 | 116篇 |
2004年 | 100篇 |
2003年 | 103篇 |
2002年 | 93篇 |
2001年 | 36篇 |
2000年 | 26篇 |
1999年 | 19篇 |
1998年 | 13篇 |
1997年 | 16篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1972年 | 4篇 |
1968年 | 9篇 |
1967年 | 3篇 |
1966年 | 5篇 |
1964年 | 6篇 |
排序方式: 共有3409条查询结果,搜索用时 15 毫秒
181.
François-Yves Dupradeau Guillaume Le Flem Jean-Michel Wieruszeski Manuel Dauchez Alain Alix Véronique Larreta-Garde Jean-Pierre Monti 《International journal of peptide research and therapeutics》1997,4(4-6):489-495
Summary
1H-NMR studies of the bovine insulin S-sulfonated B-chain are reported in H2O/D2O (9/1) and in glycerol-d
5 (5 M) using two-dimensional NMR spectroscopy. The first results show that the oxidized insulin B-chain secondary structure
differs from that of native insulin by a loss of the α-helix between the two disulfide bridges and that the glycerol favours
the structuring of the peptide. 相似文献
182.
Francisella tularensis is a highly virulent bacterium responsible for the zoonotic disease tularemia. It is a facultative intracellular pathogen that replicates in the cytoplasm of host cells, particularly in macrophages. Here we show that F. tularensis live vaccine strain (LVS) expresses a novel small RNA (sRNA), which modulates the virulence capacities of the bacterium. When this sRNA, designated FtrC (for Francisella tularensisRNA C), is expressed at high levels, F. tularensis replicates in macrophages less efficiently than the wild-type parent strain. Similarly, high expression of FtrC reduces the number of viable bacteria recovered from the spleen and liver of infected mice. Our data demonstrate that expression of gene FTL_1293 is regulated by FtrC. Furthermore, we show by in vitro gel shift assays that FtrC interacts specifically with FTL_1293 mRNA and that this happens independently of the RNA chaperone Hfq. Remarkably, FtrC interacts only with full-length FTL_1293 mRNA. These results, combined with a bioinformatic analysis, indicate that FtrC interacts with the central region of the mRNA and hence does not act by sterically hindering access of the ribosome to the mRNA. We further show that gene FTL_1293 is not required for F. tularensis virulence in vitro or in vivo, which indicates that another unidentified FtrC target modulates the virulence capacity of the bacterium. 相似文献
183.
Giovanni Benelli Nickolas G. Kavallieratos Elisa Donati Margherita Mencattelli Gabriella Bonsignori Cesare Stefanini Angelo Canale Russell H. Messing 《BioControl》2014,59(5):487-500
Aphidius colemani Viereck (Hymenoptera: Braconidae) is a pan-tropical broadly oligophagous endoparasitoid of many aphids of economic importance, including Aphis gossypii Glover and Myzus persicae (Sulzer). While the trophic interactions occurring among A. colemani and its hosts have been extensively studied, little is known about the male- and female-borne cues that guide mating dynamics. Male wing fanning has been found to play a key role in A. colemani courtship, as successful mounting of females without initial wing fanning has never been observed. In this research, we analyzed wing fanning performance and mating ability of males from three different strains of A. colemani: wasps commercially mass-reared on A. gossypii, wild wasps from parasitized A. gossypii, and wild wasps from parasitized Aphis nerii Boyer de Fonscolombe. Results showed that virgin females did not rely on particular male fanning features during mate choice. Moreover, when A. colemani individuals developed on A. gossypii, no major differences were detected in courtship and mating ability between field collected and mass-reared wasps. In contrast, courtship performance and mating success varied between wild A. colemani males reared on different hosts, with those developing on A. nerii having lower quality wing fanning performance during the mounting attempt phase, and reduced ability to compete for females with other males reared on A. gossypii. 相似文献
184.
185.
Laurent Mouchiroud Ronald E. Pachon Jie Zhang Jean‐Guillaume Dillinger Riekelt H. Houtkooper Johan Auwerx Stephen F. Vatner 《Aging cell》2015,14(6):1075-1084
The most important physiological mechanism mediating enhanced exercise performance is increased sympathetic, beta adrenergic receptor (β‐AR), and adenylyl cyclase (AC) activity. This is the first report of decreased AC activity mediating increased exercise performance. We demonstrated that AC5 disruption, that is, knock out (KO) mice, a longevity model, increases exercise performance. Importantly for its relation to longevity, exercise was also improved in old AC5 KO. The mechanism resided in skeletal muscle rather than in the heart, as confirmed by cardiac‐ and skeletal muscle‐specific AC5 KO's, where exercise performance was no longer improved by the cardiac‐specific AC5 KO, but was by the skeletal muscle‐specific AC5 KO, and there was no difference in cardiac output during exercise in AC5 KO vs. WT. Mitochondrial biogenesis was a major mechanism mediating the enhanced exercise. SIRT1, FoxO3a, MEK, and the anti‐oxidant, MnSOD were upregulated in AC5 KO mice. The improved exercise in the AC5 KO was blocked with either a SIRT1 inhibitor, MEK inhibitor, or by mating the AC5 KO with MnSOD hetero KO mice, confirming the role of SIRT1, MEK, and oxidative stress mechanisms. The Caenorhabditis elegans worm AC5 ortholog, acy‐3 by RNAi, also improved fitness, mitochondrial function, antioxidant defense, and lifespan, attesting to the evolutionary conservation of this pathway. Thus, decreasing sympathetic signaling through loss of AC5 is not only a mechanism to improve exercise performance, but is also a mechanism to improve healthful aging, as exercise also protects against diabetes, obesity, and cardiovascular disease, which all limit healthful aging. 相似文献
186.
Guillaume Gaullier Simona Miron Sabrina Pisano Rémi Buisson Yann-Va? Le?Bihan Carine Tellier-Lebègue Wala Messaoud Pierre Roblin Beatriz G. Guimar?es Robert Thai Marie-Josèphe Giraud-Panis Eric Gilson Marie-Hélène Le?Du 《Nucleic acids research》2016,44(4):1962-1976
Telomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer and aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends. Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of nucleic acid and protein interactions. RAP1 is one of the most conserved shelterin proteins although one unresolved question is how its interaction may influence TRF2 properties and regulate its capacity to bind multiple proteins. Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2. The complete interaction scheme between the full-length proteins involves a complex biphasic interaction of RAP1 that directly affects the binding properties of the assembly. These results reveal how a non-DNA binding protein can influence the properties of a DNA-binding partner by mutual conformational adjustments. 相似文献
187.
Francin PJ Guillaume C Humbert AC Pottie P Netter P Mainard D Presle N 《Journal of cellular physiology》2011,226(11):2790-2797
Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers. 相似文献
188.
van Gils MJ Edo-Matas D Bowles EJ Burger JA Stewart-Jones GB Schuitemaker H 《Journal of virology》2011,85(16):8443-8448
Analysis of longitudinally obtained HIV-1 env sequences from an individual with reported cross-reactive neutralizing activity revealed that the majority of viral variants obtained from serum between 4 and 7 years after seroconversion were unable to persist in peripheral blood. Here we show that these viral variants were more sensitive to autologous serum neutralization, had shorter envelopes with fewer potential N-linked glycosylation sites, and showed lower replication kinetics than successfully evolving HIV-1 variants. These data reflect the host selection pressures on phenotypic characteristics of HIV-1 and illustrate in detail the dynamic interaction between HIV-1 and its host's humoral immune responses. 相似文献
189.
190.