全文获取类型
收费全文 | 2072篇 |
免费 | 204篇 |
专业分类
2276篇 |
出版年
2024年 | 1篇 |
2023年 | 14篇 |
2022年 | 31篇 |
2021年 | 50篇 |
2020年 | 37篇 |
2019年 | 31篇 |
2018年 | 44篇 |
2017年 | 45篇 |
2016年 | 80篇 |
2015年 | 110篇 |
2014年 | 147篇 |
2013年 | 144篇 |
2012年 | 167篇 |
2011年 | 162篇 |
2010年 | 129篇 |
2009年 | 128篇 |
2008年 | 153篇 |
2007年 | 128篇 |
2006年 | 133篇 |
2005年 | 108篇 |
2004年 | 120篇 |
2003年 | 97篇 |
2002年 | 85篇 |
2001年 | 16篇 |
2000年 | 4篇 |
1999年 | 10篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 13篇 |
1993年 | 6篇 |
1992年 | 19篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有2276条查询结果,搜索用时 11 毫秒
21.
Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4 总被引:1,自引:0,他引:1
Aberg E Perander M Johansen B Julien C Meloche S Keyse SM Seternes OM 《The Journal of biological chemistry》2006,281(46):35499-35510
MAPK-activated protein kinase 5 (MK5) was recently identified as a physiological substrate of the atypical MAPK ERK3. Complex formation between ERK3 and MK5 results in phosphorylation and activation of MK5, concomitant stabilization of ERK3, and the nuclear exclusion of both proteins. However, ablation of ERK3 in HeLa cells using small interfering RNA or in fibroblasts derived from ERK3 null mice reduces the activity of endogenous MK5 by only 50%, suggesting additional mechanisms of MK5 regulation. Here we identify the ERK3-related kinase ERK4 as a bona fide interaction partner of MK5. Binding of ERK4 to MK5 is accompanied by phosphorylation and activation of MK5. Furthermore, complex formation also results in the relocalization of MK5 from nucleus to cytoplasm. However unlike ERK3, ERK4 is a stable protein, and its half-life is not modified by the presence or absence of MK5. Finally, although knock-down of ERK4 protein in HeLa cells reduces endogenous MK5 activity by approximately 50%, a combination of small interfering RNAs targeting both ERK4 and ERK3 causes a further reduction in the MK5 activity by more than 80%. We conclude that MK5 activation is dependent on both ERK3 and ERK4 in these cells and that these atypical MAPKs are both physiological regulators of MK5 activity. 相似文献
22.
Robert Lehmann Damien J. Lightfoot Celia Schunter Craig T. Michell Hajime Ohyanagi Katsuhiko Mineta Sylvain Foret Michael L. Berumen David J. Miller Manuel Aranda Takashi Gojobori Philip L. Munday Timothy Ravasi 《Molecular ecology resources》2019,19(3):570-585
The iconic orange clownfish, Amphiprion percula, is a model organism for studying the ecology and evolution of reef fishes, including patterns of population connectivity, sex change, social organization, habitat selection and adaptation to climate change. Notably, the orange clownfish is the only reef fish for which a complete larval dispersal kernel has been established and was the first fish species for which it was demonstrated that antipredator responses of reef fishes could be impaired by ocean acidification. Despite its importance, molecular resources for this species remain scarce and until now it lacked a reference genome assembly. Here, we present a de novo chromosome‐scale assembly of the genome of the orange clownfish Amphiprion percula. We utilized single‐molecule real‐time sequencing technology from Pacific Biosciences to produce an initial polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86 Mb. Using Hi‐C‐based chromatin contact maps, 98% of the genome assembly were placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it one of the most contiguous and complete fish genome assemblies currently available. The genome was annotated with 26,597 protein‐coding genes and contains 96% of the core set of conserved actinopterygian orthologs. The availability of this reference genome assembly as a community resource will further strengthen the role of the orange clownfish as a model species for research on the ecology and evolution of reef fishes. 相似文献
23.
Guillaume Martin Sylvain Gandon 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1548):1953-1963
The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy. 相似文献
24.
Body size or mass is one of the main factors underlying food webs structure. A large number of evolutionary models have shown that indeed, the adaptive evolution of body size (or mass) can give rise to hierarchically organised trophic levels with complex between and within trophic interactions. However, these models generally make strong arbitrary assumptions on how traits evolve, casting doubts on their robustness. In particular, biomass conversion efficiency is always considered independent of the predator and prey size, which contradicts with the literature. In this paper, we propose a general model encompassing most previous models which allows to show that relaxing arbitrary assumptions gives rise to unrealistic food webs. We then show that considering biomass conversion efficiency dependent on species size is certainly key for food webs adaptive evolution because realistic food webs can evolve, making obsolete the need of arbitrary constraints on traits' evolution. We finally conclude that, on the one hand, ecologists should pay attention to how biomass flows into food webs in models. On the other hand, we question more generally the robustness of evolutionary models for the study of food webs. 相似文献
25.
26.
Virginie Grizon Marie Dominique Legoy Sylvain Lamare 《Biocatalysis and Biotransformation》2013,31(3):177-182
It has recently been demonstrated that dried cells of Saccharomyces cerevisiae were able to produce alcohols and aldehydes in a solid/gas reactor with in situ cofactor regeneration. Since diffusion of gaseous substrates may be limited by the membrane and cell wall, cell disruption by sonication was used to improve oxidoreduction with ethanol and butyraldehyde as substrates. Results showed that partial cell disruption enhances the maximum conversion yield with the best results obtained after 2 min of sonication. Beyond this time, the ADH activity decreased. Better stability was observed in the pellet obtained after centrifugation indicating the importance of cell environment for enzyme stability. Tests on purified mitochondria showed that the ADH activity in cells was mainly cytoplasmic. The addition of oxidized cofactor did not change either the activity or the stability of the catalyst in a gaseous medium. The effect of water activity was studied on material obtained after 2 min of disruption and a reduction of critical water activity needed for revealing enzymatic activity was observed. With increasing aw, the enzyme was active at aw=0.3 while a water activity of 0.4 was required before disruption. Nevertheless, the best compromise between activity and stability was obtained in both cases for a water activity of 0.57. 相似文献
27.
Sreenath R. Palle LeAnne M. Campbell Devendra Pandeya Lorraine Puckhaber Lauren K. Tollack Sylvain Marcel Sabarinath Sundaram Robert D. Stipanovic Thomas C. Wedegaertner Lori Hinze Keerti S. Rathore 《Plant biotechnology journal》2013,11(3):296-304
Cottonseed remains a low‐value by‐product of lint production mainly due to the presence of toxic gossypol that makes it unfit for monogastrics. Ultra‐low gossypol cottonseed (ULGCS) lines were developed using RNAi knockdown of δ‐cadinene synthase gene(s) in Gossypium hirsutum. The purpose of the current study was to assess the stability and specificity of the ULGCS trait and evaluate the agronomic performance of the transgenic lines. Trials conducted over a period of 3 years show that the ULGCS trait was stable under field conditions and the foliage/floral organs of transgenic lines contained wild‐type levels of gossypol and related terpenoids. Although it was a relatively small‐scale study, we did not observe any negative effects on either the yield or quality of the fibre and seed in the transgenic lines compared with the nontransgenic parental plants. Compositional analysis was performed on the seeds obtained from plants grown in the field during 2009. As expected, the major difference between the ULGCS and wild‐type cottonseeds was in terms of their gossypol levels. With the exception of oil content, the composition of ULGCS was similar to that of nontransgenic cottonseeds. Interestingly, the ULGCS had significantly higher (4%–8%) oil content compared with the seeds from the nontransgenic parent. Field trial results confirmed the stability and specificity of the ULGCS trait suggesting that this RNAi‐based product has the potential to be commercially viable. Thus, it may be possible to enhance and expand the nutritional utility of the annual cottonseed output to fulfil the ever‐increasing needs of humanity. 相似文献
28.
Jean-Luc Montillet Nathalie Leonhardt Samuel Mondy Sylvain Tranchimand Dominique Rumeau Marie Boudsocq Ana Victoria Garcia Thierry Douki Jean Bigeard Christiane Laurière Anne Chevalier Carmen Castresana Heribert Hirt 《PLoS biology》2013,11(3)
Plant stomata function in innate immunity against bacterial invasion and abscisic acid (ABA) has been suggested to regulate this process. Using genetic, biochemical, and pharmacological approaches, we demonstrate that (i) the Arabidopsis thaliana nine-specific-lipoxygenase encoding gene, LOX1, which is expressed in guard cells, is required to trigger stomatal closure in response to both bacteria and the pathogen-associated molecular pattern flagellin peptide flg22; (ii) LOX1 participates in stomatal defense; (iii) polyunsaturated fatty acids, the LOX substrates, trigger stomatal closure; (iv) the LOX products, fatty acid hydroperoxides, or reactive electrophile oxylipins induce stomatal closure; and (v) the flg22-mediated stomatal closure is conveyed by both LOX1 and the mitogen-activated protein kinases MPK3 and MPK6 and involves salicylic acid whereas the ABA-induced process depends on the protein kinases OST1, MPK9, or MPK12. Finally, we show that the oxylipin and the ABA pathways converge at the level of the anion channel SLAC1 to regulate stomatal closure. Collectively, our results demonstrate that early biotic signaling in guard cells is an ABA-independent process revealing a novel function of LOX1-dependent stomatal pathway in plant immunity. 相似文献
29.
André M. Ribeiro-dos-Santos Jorge Estefano Santana de Souza Renan Almeida Dayse O. Alencar Maria Silvanira Barbosa Leonor Gusm?o Wilson A. Silva Jr Sandro J. de Souza Artur Silva ?ndrea Ribeiro-dos-Santos Sylvain Darnet Sidney Santos 《PloS one》2013,8(12)
The emergence of next-generation sequencing technologies allowed access to the vast amounts of information that are contained in the human genome. This information has contributed to the understanding of individual and population-based variability and improved the understanding of the evolutionary history of different human groups. However, the genome of a representative of the Amerindian populations had not been previously sequenced. Thus, the genome of an individual from a South American tribe was completely sequenced to further the understanding of the genetic variability of Amerindians. A total of 36.8 giga base pairs (Gbp) were sequenced and aligned with the human genome. These Gbp corresponded to 95.92% of the human genome with an estimated miscall rate of 0.0035 per sequenced bp. The data obtained from the alignment were used for SNP (single-nucleotide) and INDEL (insertion-deletion) calling, which resulted in the identification of 502,017 polymorphisms, of which 32,275 were potentially new high-confidence SNPs and 33,795 new INDELs, specific of South Native American populations. The authenticity of the sample as a member of the South Native American populations was confirmed through the analysis of the uniparental (maternal and paternal) lineages. The autosomal comparison distinguished the investigated sample from others continental populations and revealed a close relation to the Eastern Asian populations and Aboriginal Australian. Although, the findings did not discard the classical model of America settlement; it brought new insides to the understanding of the human population history. The present study indicates a remarkable genetic variability in human populations that must still be identified and contributes to the understanding of the genetic variability of South Native American populations and of the human populations history. 相似文献
30.
Pierre-Benoit Pagès Olivier Facy Pierre Mordant Sylvain Ladoire Guy Magnin Francois Lokiec Francois Ghiringhelli Alain Bernard 《PloS one》2013,8(3)