全文获取类型
收费全文 | 10515篇 |
免费 | 907篇 |
国内免费 | 113篇 |
专业分类
11535篇 |
出版年
2023年 | 65篇 |
2022年 | 134篇 |
2021年 | 293篇 |
2020年 | 149篇 |
2019年 | 233篇 |
2018年 | 274篇 |
2017年 | 211篇 |
2016年 | 309篇 |
2015年 | 524篇 |
2014年 | 671篇 |
2013年 | 807篇 |
2012年 | 903篇 |
2011年 | 856篇 |
2010年 | 552篇 |
2009年 | 490篇 |
2008年 | 627篇 |
2007年 | 604篇 |
2006年 | 570篇 |
2005年 | 545篇 |
2004年 | 484篇 |
2003年 | 456篇 |
2002年 | 445篇 |
2001年 | 139篇 |
2000年 | 128篇 |
1999年 | 152篇 |
1998年 | 106篇 |
1997年 | 70篇 |
1996年 | 66篇 |
1995年 | 69篇 |
1994年 | 42篇 |
1993年 | 43篇 |
1992年 | 46篇 |
1991年 | 33篇 |
1990年 | 33篇 |
1989年 | 41篇 |
1988年 | 25篇 |
1987年 | 37篇 |
1986年 | 25篇 |
1985年 | 26篇 |
1984年 | 15篇 |
1983年 | 26篇 |
1982年 | 15篇 |
1980年 | 20篇 |
1979年 | 19篇 |
1978年 | 16篇 |
1977年 | 17篇 |
1976年 | 12篇 |
1975年 | 13篇 |
1974年 | 12篇 |
1972年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
71.
Mazon H Marcillat O Forest E Vial C 《Protein science : a publication of the Protein Society》2004,13(2):476-486
Creatine kinase (CK) isoenzymes catalyse the reversible transfer of a phosphoryl group from ATP onto creatine. This reaction plays a very important role in the regulation of intracellular ATP concentrations in excitable tissues. CK isoenzymes are highly resistant to proteases in native conditions. To appreciate localized backbone dynamics, kinetics of amide hydrogen exchange with deuterium was measured by pulse-labeling the dimeric cytosolic muscle CK isoenzyme. Upon exchange, the protein was digested with pepsin, and the deuterium content of the resulting peptides was determined by liquid chromatography coupled to mass spectrometry (MS). The deuteration kinetics of 47 peptides identified by MS/MS and covering 96% of the CK backbone were analyzed. Four deuteration patterns have been recognized: The less deuterated peptides are located in the saddle-shaped core of CK, whereas most of the highly deuterated peptides are close to the surface and located around the entrance to the active site. Their exchange kinetics are discussed by comparison with the known secondary and tertiary structures of CK with the goal to reveal the conformational dynamics of the protein. Some of the observed dynamic motions may be linked to the conformational changes associated with substrate binding and catalytic mechanism. 相似文献
72.
Hanon C Bernard O Rabate M Claire T 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(6):1551-1557
The purpose of this study was to analyze 2 different long-sprint training programs (TPs) of equal total work load, completed either with short recovery (SR) or long recovery (LR) between sets and to compare the effects of 6 long-sprint training sessions (TSs) conducted over a 2-week period on a 300-m performance. Fourteen trained subjects performed 3 pretraining maximal sprints (50-, 100-, and 300-m), were paired according to their 300-m performance, and randomly allocated to an LR or SR group, which performed 6 TSs consisting of sets of 150, 200, or 250 m. The recovery in the LR group was double that of the SR group. During the third TS and the 300-m pretest and posttest, blood pH, bicarbonate concentration ([HCO??]), excess-base (EB), and lactate concentration were recorded. Compared with a similar TS performed with SR, the LR training tends to induce a greater alteration of the acid-base balance: pH: 7.09 ± 0.08 (LR) and 7.14 ± 0.05 (SR) (p = 0.10), [HCO??]: 7.8 ± 1.9 (LR) and 9.6 ± 2.7 (SR) (p = 0.04), and EB: -21.1 ± 3.8 (LR) and -17.7 ± 2.8 (SR) (p = 0.11). A significant improvement in the 300-m performance between pre-TP and post-TP (42.45 ± 2.64 vs. 41.52 ± 2.45, p = 0.01) and significant decreases in pH (p < 0.01), EB (p < 0.001) and increase in [La] (p < 0.001) have been observed post-TP compared with those pre-TP. Although sprint training with longer recovery induces higher metabolic disturbances, both sprint training regimens allow a similar 300-m performance improvement with no concomitant significant progress in the 50- and 100-m performance. 相似文献
73.
74.
Plants,microorganisms, and soil temperatures contribute to a decrease in methane fluxes on a drained Arctic floodplain 下载免费PDF全文
Min Jung Kwon Felix Beulig Iulia Ilie Marcus Wildner Kirsten Küsel Lutz Merbold Miguel D. Mahecha Nikita Zimov Sergey A. Zimov Martin Heimann Edward A. G. Schuur Joel E. Kostka Olaf Kolle Ines Hilke Mathias Göckede 《Global Change Biology》2017,23(6):2396-2412
As surface temperatures are expected to rise in the future, ice‐rich permafrost may thaw, altering soil topography and hydrology and creating a mosaic of wet and dry soil surfaces in the Arctic. Arctic wetlands are large sources of CH4, and investigating effects of soil hydrology on CH4 fluxes is of great importance for predicting ecosystem feedback in response to climate change. In this study, we investigate how a decade‐long drying manipulation on an Arctic floodplain influences CH4‐associated microorganisms, soil thermal regimes, and plant communities. Moreover, we examine how these drainage‐induced changes may then modify CH4 fluxes in the growing and nongrowing seasons. This study shows that drainage substantially lowered the abundance of methanogens along with methanotrophic bacteria, which may have reduced CH4 cycling. Soil temperatures of the drained areas were lower in deep, anoxic soil layers (below 30 cm), but higher in oxic topsoil layers (0–15 cm) compared to the control wet areas. This pattern of soil temperatures may have reduced the rates of methanogenesis while elevating those of CH4 oxidation, thereby decreasing net CH4 fluxes. The abundance of Eriophorum angustifolium, an aerenchymatous plant species, diminished significantly in the drained areas. Due to this decrease, a higher fraction of CH4 was alternatively emitted to the atmosphere by diffusion, possibly increasing the potential for CH4 oxidation and leading to a decrease in net CH4 fluxes compared to a control site. Drainage lowered CH4 fluxes by a factor of 20 during the growing season, with postdrainage changes in microbial communities, soil temperatures, and plant communities also contributing to this reduction. In contrast, we observed CH4 emissions increased by 10% in the drained areas during the nongrowing season, although this difference was insignificant given the small magnitudes of fluxes. This study showed that long‐term drainage considerably reduced CH4 fluxes through modified ecosystem properties. 相似文献
75.
Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors 下载免费PDF全文
Sii-Felice K Etienne O Hoffschir F Mathieu C Riou L Barroca V Haton C Arwert F Fouchet P Boussin FD Mouthon MA 《The EMBO journal》2008,27(5):770-781
Although brain development abnormalities and brain cancer predisposition have been reported in some Fanconi patients, the possible role of Fanconi DNA repair pathway during neurogenesis is unclear. We thus addressed the role of fanca and fancg, which are involved in the activation of Fanconi pathway, in neural stem and progenitor cells during brain development and adult neurogenesis. Fanca(-/-) and fancg(-/-) mice presented with microcephalies and a decreased neuronal production in developing cortex and adult brain. Apoptosis of embryonic neural progenitors, but not that of postmitotic neurons, was increased in the neocortex of fanca(-/-) and fancg(-/-) mice and was correlated with chromosomal instability. In adult Fanconi mice, we showed a reduced proliferation of neural progenitor cells related to apoptosis and accentuated neural stem cells exhaustion with ageing. In addition, embryonic and adult Fanconi neural stem cells showed a reduced capacity to self-renew in vitro. Our study demonstrates a critical role for Fanconi pathway in neural stem and progenitor cells during developmental and adult neurogenesis. 相似文献
76.
77.
78.
Yanwen Jiang David Redmond Kui Nie Ken W Eng Thomas Clozel Peter Martin Leonard HC Tan Ari M Melnick Wayne Tam Olivier Elemento 《Genome biology》2014,15(8)
Background
Molecular mechanisms associated with frequent relapse of diffuse large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how primary tumor clonal heterogeneity contributes to relapse. Here, we explore unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation - to address this question.Results
We performed high-throughput sequencing of rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among which 7 pairs were further characterized by exome sequencing. We identify two distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode in which clonally related diagnosis and relapse tumors diverged early and developed in parallel; and a late-divergent mode in which relapse tumors developed directly from diagnosis tumors with minor divergence. By examining mutation patterns in the context of phylogenetic information provided by VDJ junctions, we identified mutations in epigenetic modifiers such as KMT2D as potential early driving events in lymphomagenesis and immune escape alterations as relapse-associated events.Conclusions
Altogether, our study for the first time provides important evidence that DLBCL relapse may result from multiple, distinct tumor evolutionary mechanisms, providing rationale for therapies for each mechanism. Moreover, this study highlights the urgent need to understand the driving roles of epigenetic modifier mutations in lymphomagenesis, and immune surveillance factor genetic lesions in relapse.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0432-0) contains supplementary material, which is available to authorized users. 相似文献79.
Géraldine Carlier Alicia Maugein Corinne Cordier Séverine Pechberty Meriem Garfa-Traoré Patrick Martin Rapha?l Scharfmann Olivier Albagli 《PloS one》2014,9(9)
Regulation of cell cycle in beta cells is poorly understood, especially in humans. We exploited here the recently described human pancreatic beta cell line EndoC-βH2 to set up experimental systems for cell cycle studies. We derived 2 populations from EndoC-βH2 cells that stably harbor the 2 genes encoding the Fucci fluorescent indicators of cell cycle, either from two vectors, or from a unique bicistronic vector. In proliferating non-synchronized cells, the 2 Fucci indicators revealed cells in the expected phases of cell cycle, with orange and green cells being in G1 and S/G2/M cells, respectively, and allowed the sorting of cells in different substeps of G1. The Fucci indicators also faithfully red out alterations in human beta cell proliferative activity since a mitogen-rich medium decreased the proportion of orange cells and inflated the green population, while reciprocal changes were observed when cells were induced to cease proliferation and increased expression of some beta cell genes. In the last situation, acquisition of a more differentiated beta cell phenotype correlates with an increased intensity in orange fluorescence. Hence Fucci beta cell lines provide new tools to address important questions regarding human beta cell cycle and differentiation. 相似文献
80.
Nawel Selami Marie-Christine Auriac Olivier Catrice Delphine Capela Meriem Kaid-Harche Ton Timmers 《Plant and Soil》2014,374(1-2):109-119