全文获取类型
收费全文 | 22015篇 |
免费 | 1536篇 |
国内免费 | 9篇 |
专业分类
23560篇 |
出版年
2024年 | 19篇 |
2023年 | 127篇 |
2022年 | 311篇 |
2021年 | 580篇 |
2020年 | 351篇 |
2019年 | 471篇 |
2018年 | 593篇 |
2017年 | 479篇 |
2016年 | 809篇 |
2015年 | 1218篇 |
2014年 | 1346篇 |
2013年 | 1666篇 |
2012年 | 1949篇 |
2011年 | 1892篇 |
2010年 | 1175篇 |
2009年 | 1017篇 |
2008年 | 1376篇 |
2007年 | 1288篇 |
2006年 | 1180篇 |
2005年 | 1083篇 |
2004年 | 983篇 |
2003年 | 930篇 |
2002年 | 754篇 |
2001年 | 119篇 |
2000年 | 115篇 |
1999年 | 136篇 |
1998年 | 129篇 |
1997年 | 116篇 |
1996年 | 91篇 |
1995年 | 87篇 |
1994年 | 94篇 |
1993年 | 91篇 |
1992年 | 62篇 |
1991年 | 71篇 |
1990年 | 69篇 |
1989年 | 51篇 |
1988年 | 53篇 |
1987年 | 40篇 |
1986年 | 47篇 |
1985年 | 52篇 |
1984年 | 45篇 |
1983年 | 45篇 |
1982年 | 34篇 |
1981年 | 44篇 |
1980年 | 29篇 |
1979年 | 35篇 |
1978年 | 32篇 |
1977年 | 33篇 |
1976年 | 26篇 |
1975年 | 22篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Background and Aims
Leaf hydraulic properties are strongly linked with transpiration and photosynthesis in many species. However, it is not known if gas exchange and hydraulics will have co-ordinated responses to climate change. The objective of this study was to investigate the responses of leaf hydraulic conductance (Kleaf) in Glycine max (soybean) to growth at elevated [CO2] and increased temperature compared with the responses of leaf gas exchange and leaf water status.Methods
Two controlled-environment growth chamber experiments were conducted with soybean to measure Kleaf, stomatal conductance (gs) and photosynthesis (A) during growth at elevated [CO2] and temperature relative to ambient levels. These results were validated with field experiments on soybean grown under free-air elevated [CO2] (FACE) and canopy warming.Key results
In chamber studies, Kleaf did not acclimate to growth at elevated [CO2], even though stomatal conductance decreased and photosynthesis increased. Growth at elevated temperature also did not affect Kleaf, although gs and A showed significant but inconsistent decreases. The lack of response of Kleaf to growth at increased [CO2] and temperature in chamber-grown plants was confirmed with field-grown soybean at a FACE facility.Conclusions
Leaf hydraulic and leaf gas exchange responses to these two climate change factors were not strongly linked in soybean, although gs responded to [CO2] and increased temperature as previously reported. This differential behaviour could lead to an imbalance between hydraulic supply and transpiration demand under extreme environmental conditions likely to become more common as global climate continues to change. 相似文献992.
Gianguglielmo Zehender Erika Ebranati Renata Shkjezi Anna Papa Camilla Luzzago Elena Gabanelli Alessandra Lo Presti Alessia Lai Giovanni Rezza Massimo Galli Silvia Bino Massimo Ciccozzi 《PloS one》2013,8(11)
Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10-4 (95%HPD=1.6 and 4.7 x 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe. 相似文献
993.
Kevin A. Lawson Colin J. Teteak Junhui Zou Jacques Hacquebord Andrew Ghatan Anna Zielinska-Kwiatkowska Russell J. Fernandes Howard A. Chansky Liu Yang 《The Journal of biological chemistry》2013,288(45):32119-32125
The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis. 相似文献
994.
995.
996.
Ying-Lien Chen Virginia N. Lehman Anna F. Averette John R. Perfect Joseph Heitman 《PloS one》2013,8(3)
The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future. 相似文献
997.
Anna V. Miller Mark A. Hicks Wataru Nakajima Amanda C. Richardson Jolene J. Windle Hisashi Harada 《PloS one》2013,8(4)
Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim−/− MEFs (mouse embryonic fibroblasts), the bim−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak
−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax−/− MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance. 相似文献
998.
DNA double strand breaks (DSBs) are potentially serious chromosomal lesions. However, cells sometimes deliberately cleave their own DNA to facilitate certain chromosomal processes, and there is much interest in how such self-inflicted breaks are effectively managed. Eukaryotic DSBs occur in the context of chromatin and the RSC chromatin-remodeling ATPase complex has been shown to promote DSB repair at the budding yeast MAT locus DSB, created by the HO endonuclease during mating type switching. We show that the role of RSC at MAT is highly specialized. The Rsc1p subunit of RSC directs nucleosome sliding immediately after DSB creation at both MAT and generally and is required for efficient DNA damage-induced histone H2A phosphorylation and strand resection during repair by homologous recombination. However, the Rsc2p and Rsc7p subunits are additionally required to set up a basal MAT locus structure. This RSC-dependent chromatin structure at MAT ensures accessibility to the HO endonuclease. The RSC complex therefore has chromatin remodeling roles both before and after DSB induction at MAT, promoting both DNA cleavage and subsequent repair. 相似文献
999.
1000.
Leonardo Vargas Beston F Nore Anna Berglof Juhana E Heinonen Pekka T Mattsson C I Edvard Smith Abdalla J Mohamed 《The Journal of biological chemistry》2002,277(11):9351-9357
Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82--101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation. 相似文献