全文获取类型
收费全文 | 1473篇 |
免费 | 114篇 |
国内免费 | 3篇 |
专业分类
1590篇 |
出版年
2023年 | 16篇 |
2022年 | 12篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 18篇 |
2018年 | 47篇 |
2017年 | 23篇 |
2016年 | 43篇 |
2015年 | 91篇 |
2014年 | 92篇 |
2013年 | 99篇 |
2012年 | 102篇 |
2011年 | 116篇 |
2010年 | 69篇 |
2009年 | 59篇 |
2008年 | 91篇 |
2007年 | 83篇 |
2006年 | 65篇 |
2005年 | 65篇 |
2004年 | 60篇 |
2003年 | 58篇 |
2002年 | 38篇 |
2001年 | 14篇 |
2000年 | 16篇 |
1999年 | 19篇 |
1997年 | 6篇 |
1992年 | 16篇 |
1991年 | 21篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 15篇 |
1985年 | 23篇 |
1984年 | 13篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1971年 | 6篇 |
1970年 | 7篇 |
1965年 | 3篇 |
排序方式: 共有1590条查询结果,搜索用时 0 毫秒
971.
Flori L Gao Y Laloë D Lemonnier G Leplat JJ Teillaud A Cossalter AM Laffitte J Pinton P de Vaureix C Bouffaud M Mercat MJ Lefèvre F Oswald IP Bidanel JP Rogel-Gaillard C 《PloS one》2011,6(7):e22717
Background
Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual''s immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment.Methodology/Principal Findings
Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.10.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs.Conclusions/Significance
Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits. 相似文献
972.
Glycogen storage disease type II or Pompe disease (GSD II, MIM 232300) is a rare inherited metabolic myopathy caused by a deficiency of lysosomal acid α-glucosidase or acid maltase (GAA; EC 3.2.1.20), resulting in a massive lysosomal glycogen accumulation in cardiac and skeletal muscles. Affected individuals exhibit either severe hypotonia associated with hypertrophic cardiomyopathy (infantile forms) or progressive muscle weakness (late-onset forms). Even if enzyme replacement therapy has recently become a standard treatment, it suffers from several limitations. This review will present the main results of enzyme replacement therapy and the recent findings concerning alternative treatments for Pompe disease, such as gene therapy, enzyme enhancement therapy, and substrate reduction therapy. 相似文献
973.
974.
Félix Legendre Neal Cody Carole Iampietro Julie Bergalet Fabio Alexis Lefebvre Ga?l Moquin-Beaudry Olivia Zhang Xiaofeng Wang Eric Lécuyer 《Journal of visualized experiments : JoVE》2013,(71)
Assessing the expression pattern of a gene, as well as the subcellular localization properties of its transcribed RNA, are key features for understanding its biological function during development. RNA in situ hybridization (RNA-ISH) is a powerful method used for visualizing RNA distribution properties, be it at the organismal, cellular or subcellular levels 1. RNA-ISH is based on the hybridization of a labeled nucleic acid probe (e.g. antisense RNA, oligonucleotides) complementary to the sequence of an mRNA or a non-coding RNA target of interest 2. As the procedure requires primary sequence information alone to generate sequence-specific probes, it can be universally applied to a broad range of organisms and tissue specimens 3. Indeed, a number of large-scale ISH studies have been implemented to document gene expression and RNA localization dynamics in various model organisms, which has led to the establishment of important community resources 4-11. While a variety of probe labeling and detection strategies have been developed over the years, the combined usage of fluorescently-labeled detection reagents and enzymatic signal amplification steps offer significant enhancements in the sensitivity and resolution of the procedure 12. Here, we describe an optimized fluorescent in situ hybridization method (FISH) employing tyramide signal amplification (TSA) to visualize RNA expression and localization dynamics in staged Drosophila embryos. The procedure is carried out in 96-well PCR plate format, which greatly facilitates the simultaneous processing of large numbers of samples. 相似文献
975.
Marbaix AY Noël G Detroux AM Vertommen D Van Schaftingen E Linster CL 《The Journal of biological chemistry》2011,286(48):41246-41252
The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. We report the molecular identification of the eukaryotic dehydratase that repairs these nucleotides and show that this enzyme (Carkd in mammals, YKL151C in yeast) catalyzes the dehydration of the S form of NADHX and NADPHX, at the expense of ATP, which is converted to ADP. Surprisingly, the Escherichia coli homolog, YjeF, a bidomain protein, catalyzes a similar reaction, but using ADP instead of ATP. The latter reaction is ascribable to the C-terminal domain of YjeF. This represents an unprecedented example of orthologous enzymes using either ADP or ATP as phosphoryl donor. We also show that eukaryotic proteins homologous to the N-terminal domain of YjeF (apolipoprotein A-1-binding protein (AIBP) in mammals, YNL200C in yeast) catalyze the epimerization of the S and R forms of NAD(P)HX, thereby allowing, in conjunction with the energy-dependent dehydratase, the repair of both epimers of NAD(P)HX. Both enzymes are very widespread in eukaryotes, prokaryotes, and archaea, which together with the ADP dependence of the dehydratase in some species indicates the ancient origin of this repair system. 相似文献
976.
977.
Spatial synchrony in population dynamics has been identified in most taxonomic groups. Numerous studies have reported varying levels of spatial synchrony among closely‐related species, suggesting that species' characteristics may play a role in determining the level of synchrony. However, few studies have attempted to relate this synchrony to the ecological characteristics and/or life‐history traits of species. Yet, as to some extent the extinction risk may be related to synchrony patterns, identifying a link between species' characteristics and spatial synchrony is crucial, and would help us to define effective conservation planning. Here, we investigated whether species attributes and temperature synchrony (i.e. a proxy of the Moran effect) account for the differences in spatial population synchrony observed in 27 stream fish species in France. After measuring and testing the level of synchrony for each species, we performed a comparative analysis to detect the phylogenetic signal of these levels, and to construct various multi‐predictor models with species traits and temperature synchrony as covariates, while taking phylogenetic relatedness into account. We then performed model averaging on selected models to take model uncertainty into account in our parameter estimates. Fifteen of the 27 species displayed a significant level of synchrony. Synchrony was weak, but highly variable between species, and was not conserved across the phylogeny. We found that some species' characteristics significantly influenced synchrony levels. Indeed, the average model indicated that species associated with greater dispersal abilities, lower thermal tolerance, and opportunistic strategy displayed a higher degree of synchrony. These findings indicate that phylogeny and spatial temperature synchrony do not provide information pertinent for explaining the variations in species' synchrony levels, whereas the dispersal abilities, the life‐history strategies and the upper thermal tolerance limits of species do appear to be quite reliable predictors of synchrony levels. 相似文献
978.
The origin and early diversification of decapod crustaceans and their expansion from marine to continental environments are key events in arthropod evolution. Rare fossil decapods are known from the Palaeozoic, and the earliest eumalacostracans with undoubted decapod affinities are the Late Devonian Palaeopalaemon and Aciculopoda, found in offshore marine deposits. Here, we describe a new species of the shrimp Tealliocaris found in floodplain and temporary pond deposits from the Famennian (Late Devonian) of Belgium, together with a rare Palaeozoic assemblage of other crustaceans (conchostracans, notostracans and anostracans) and chelicerates (eurypterids). Tealliocaris walloniensis sp. nov. documents the earliest occurrence of continental decapod crustaceans and indicates that decapods have been part of continental ecosystems at least since the Late Devonian. 相似文献
979.
Adrien Candat Ga?l Paszkiewicz Martine Neveu Romain Gautier David C. Logan Marie-Hélène Avelange-Macherel David Macherel 《The Plant cell》2014,26(7):3148-3166
Late embryogenesis abundant (LEA) proteins are hydrophilic, mostly intrinsically
disordered proteins, which play major roles in desiccation tolerance. In
Arabidopsis thaliana, 51 genes encoding LEA proteins clustered
into nine families have been inventoried. To increase our understanding of the yet
enigmatic functions of these gene families, we report the subcellular location of
each protein. Experimental data highlight the limits of in silico predictions for
analysis of subcellular localization. Thirty-six LEA proteins localized to the
cytosol, with most being able to diffuse into the nucleus. Three proteins were
exclusively localized in plastids or mitochondria, while two others were found dually
targeted to these organelles. Targeting cleavage sites could be determined for five
of these proteins. Three proteins were found to be endoplasmic reticulum (ER) residents, two were vacuolar, and two were
secreted. A single protein was identified in pexophagosomes. While most LEA protein
families have a unique subcellular localization, members of the LEA_4 family are
widely distributed (cytosol, mitochondria, plastid, ER, and pexophagosome) but share the presence of the class A
α-helix motif. They are thus expected to establish interactions with various
cellular membranes under stress conditions. The broad subcellular distribution of LEA
proteins highlights the requirement for each cellular compartment to be provided with
protective mechanisms to cope with desiccation or cold stress. 相似文献
980.
Nazia Perveen Sébastien Barot Gaël Alvarez Katja Klumpp Raphael Martin Alain Rapaport Damien Herfurth Frédérique Louault Sébastien Fontaine 《Global Change Biology》2014,20(4):1174-1190
Integration of the priming effect (PE) in ecosystem models is crucial to better predict the consequences of global change on ecosystem carbon (C) dynamics and its feedbacks on climate. Over the last decade, many attempts have been made to model PE in soil. However, PE has not yet been incorporated into any ecosystem models. Here, we build plant/soil models to explore how PE and microbial diversity influence soil/plant interactions and ecosystem C and nitrogen (N) dynamics in response to global change (elevated CO2 and atmospheric N depositions). Our results show that plant persistence, soil organic matter (SOM) accumulation, and low N leaching in undisturbed ecosystems relies on a fine adjustment of microbial N mineralization to plant N uptake. This adjustment can be modeled in the SYMPHONY model by considering the destruction of SOM through PE, and the interactions between two microbial functional groups: SOM decomposers and SOM builders. After estimation of parameters, SYMPHONY provided realistic predictions on forage production, soil C storage and N leaching for a permanent grassland. Consistent with recent observations, SYMPHONY predicted a CO2‐induced modification of soil microbial communities leading to an intensification of SOM mineralization and a decrease in the soil C stock. SYMPHONY also indicated that atmospheric N deposition may promote SOM accumulation via changes in the structure and metabolic activities of microbial communities. Collectively, these results suggest that the PE and functional role of microbial diversity may be incorporated in ecosystem models with a few additional parameters, improving accuracy of predictions. 相似文献