全文获取类型
收费全文 | 486篇 |
免费 | 50篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 36篇 |
2014年 | 31篇 |
2013年 | 26篇 |
2012年 | 54篇 |
2011年 | 40篇 |
2010年 | 30篇 |
2009年 | 22篇 |
2008年 | 30篇 |
2007年 | 34篇 |
2006年 | 21篇 |
2005年 | 30篇 |
2004年 | 22篇 |
2003年 | 18篇 |
2002年 | 19篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 8篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有536条查询结果,搜索用时 15 毫秒
11.
Eric Allan Wolfgang W. Weisser Markus Fischer Ernst-Detlef Schulze Alexandra Weigelt Christiane Roscher Jussi Baade Romain L. Barnard Holger Beßler Nina Buchmann Anne Ebeling Nico Eisenhauer Christof Engels Alexander J. F. Fergus Gerd Gleixner Marlén Gubsch Stefan Halle Alexandra M. Klein Ilona Kertscher Annely Kuu Markus Lange Xavier Le Roux Sebastian T. Meyer Varvara D. Migunova Alexandru Milcu Pascal A. Niklaus Yvonne Oelmann Esther Pašalić Jana S. Petermann Franck Poly Tanja Rottstock Alexander C. W. Sabais Christoph Scherber Michael Scherer-Lorenzen Stefan Scheu Sibylle Steinbeiss Guido Schwichtenberg Vicky Temperton Teja Tscharntke Winfried Voigt Wolfgang Wilcke Christian Wirth Bernhard Schmid 《Oecologia》2013,173(1):223-237
In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination. 相似文献
12.
13.
Vicky Wang-Wei Tsai Laurence Macia Heiko Johnen Tamara Kuffner Rakesh Manadhar Sebastian Beck J?rgensen Ka Ki Michelle Lee-Ng Hong Ping Zhang Liyun Wu Christopher Peter Marquis Lele Jiang Yasmin Husaini Shu Lin Herbert Herzog David A. Brown Amanda Sainsbury Samuel N. Breit 《PloS one》2013,8(2)
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage. 相似文献
14.
Erica L. Gorenberg Sofia Massaro Tieze Betül Yücel Helen R. Zhao Vicky Chou Gregory S. Wirak Susumu Tomita TuKiet T. Lam Sreeganga S. Chandra 《PLoS biology》2022,20(3)
Loss-of-function mutations in the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) cause neuronal ceroid lipofuscinosis (NCL), a devastating neurodegenerative disease. The substrates of PPT1 are largely undescribed, posing a limitation on molecular dissection of disease mechanisms and therapeutic development. Here, we provide a resource identifying >100 novel PPT1 substrates. We utilized Acyl Resin-Assisted Capture (Acyl RAC) and mass spectrometry to identify proteins with increased in vivo palmitoylation in PPT1 knockout (KO) mouse brains. We then validated putative substrates through direct depalmitoylation with recombinant PPT1. This stringent screen elucidated diverse PPT1 substrates at the synapse, including channels and transporters, G-protein–associated molecules, endo/exocytic components, synaptic adhesion molecules, and mitochondrial proteins. Cysteine depalmitoylation sites in transmembrane PPT1 substrates frequently participate in disulfide bonds in the mature protein. We confirmed that depalmitoylation plays a role in disulfide bond formation in a tertiary screen analyzing posttranslational modifications (PTMs). Collectively, these data highlight the role of PPT1 in mediating synapse functions, implicate molecular pathways in the etiology of NCL and other neurodegenerative diseases, and advance our basic understanding of the purpose of depalmitoylation.Unbiased proteomics with acyl resin-assisted capture reveals diverse novel substrates of the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) at the synapse, with potential implications for the pathogenesis of neuronal ceroid lipofuscinosis, disulfide bond formation, synaptic adhesion and additional critical synaptic functions. 相似文献
15.
Kung Ban Sandra Duffy Yelena Khakham Vicky M. Avery Andrew Hughes Oliver Montagnat Kasiram Katneni Eileen Ryan Jonathan B. Baell 《Bioorganic & medicinal chemistry letters》2010,20(20):6024-6029
We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to several thousand-fold lower toxicity to mammalian cells. They are equipotent against chloroquine-resistant strains of P. falciparum. 相似文献
16.
Papaioannou A Manos M Karkabounas S Liasko R Evangelou AM Correia I Kalfakakou V Pessoa JC Kabanos T 《Journal of inorganic biochemistry》2004,98(6):959-968
Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys- ligand to the VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV-visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover, the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with l-cysteine and VIVOSO4.5H2O exhibited metastases. 相似文献
17.
The mechanisms underlying somatic hypermutation (SHM) and class switch recombination (CSR) have been the subject of much debate. Recent studies from the Neuberger and Honjo labs have lent insight into these distinct processes, and we discuss a new, comprehensive model for how AID, uracil DNA glycosylase (UNG) and the mismatch repair system function in both SHM and CSR. 相似文献
18.
Tsipouri V Curtin JA Nolan PM Vizor L Parsons CA Clapham CM Latham ID Rooke LJ Martin JE Peters J Hunter AJ Rogers D Rastan S Brown SD Fisher EM Spurr NK Gray IC 《Comparative and Functional Genomics》2004,5(2):123-127
Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. 相似文献
19.
Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sung VM Shimodaira S Doughty AL Picchio GR Can H Yen TS Lindsay KL Levine AM Lai MM 《Journal of virology》2003,77(3):2134-2146
20.
In vitro RNA replication directed by replicase complexes isolated from the subgenomic replicon cells of hepatitis C virus 总被引:2,自引:0,他引:2
Replication of hepatitis C virus (HCV) RNA in virus-infected cells is believed to be catalyzed by viral replicase complexes (RCs), which may consist of various virally encoded nonstructural proteins and host factors. In this study, we characterized the RC activity of a crude membrane fraction isolated from HCV subgenomic replicon cells. The RC preparation was able to use endogenous replicon RNA as a template to synthesize both single-stranded (ss) and double-stranded (ds) RNA products. Divalent cations (Mg2+ and Mn2+) showed different effects on RNA synthesis. Mg2+ ions stimulated the synthesis of ss RNA but had little effect on the synthesis of ds RNA. In contrast, Mn2+ ions enhanced primarily the synthesis of ds RNA. Interestingly, ss RNA could be synthesized under certain conditions in the absence of ds RNA, and vice versa, suggesting that the ss and ds RNA were derived either from different forms of replicative intermediates or from different RCs. Pulse-chase analysis showed that radioactivity incorporated into the ss RNA was chased into the ds RNA and other larger RNA species. This observation indicated that the newly synthesized ss RNA could serve as a template for a further round of RNA synthesis. Finally, 3' deoxyribonucleoside triphosphates were able to inhibit RNA synthesis in this cell-free system, presumably through chain termination, with 3' dGTP having the highest potency. Establishment of the replicase assay will facilitate the identification and evaluation of potential inhibitors that would act against the entire RC of HCV. 相似文献