全文获取类型
收费全文 | 2788篇 |
免费 | 281篇 |
国内免费 | 1篇 |
出版年
2023年 | 29篇 |
2022年 | 13篇 |
2021年 | 101篇 |
2020年 | 67篇 |
2019年 | 78篇 |
2018年 | 92篇 |
2017年 | 84篇 |
2016年 | 127篇 |
2015年 | 166篇 |
2014年 | 191篇 |
2013年 | 235篇 |
2012年 | 307篇 |
2011年 | 280篇 |
2010年 | 140篇 |
2009年 | 128篇 |
2008年 | 170篇 |
2007年 | 169篇 |
2006年 | 144篇 |
2005年 | 106篇 |
2004年 | 93篇 |
2003年 | 92篇 |
2002年 | 85篇 |
2001年 | 28篇 |
2000年 | 25篇 |
1999年 | 17篇 |
1998年 | 12篇 |
1997年 | 15篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1956年 | 2篇 |
排序方式: 共有3070条查询结果,搜索用时 187 毫秒
1.
2.
Guillaume Laflamme Thierry Tremblay-Boudreault Marc-André Roy Parker Andersen éric Bonneil Kaleem Atchia Pierre Thibault Damien D'Amours Benjamin H. Kwok 《The Journal of biological chemistry》2014,289(40):27418-27431
Structural maintenance of chromosome (SMC) proteins are key organizers of chromosome architecture and are essential for genome integrity. They act by binding to chromatin and connecting distinct parts of chromosomes together. Interestingly, their potential role in providing connections between chromatin and the mitotic spindle has not been explored. Here, we show that yeast SMC proteins bind directly to microtubules and can provide a functional link between microtubules and DNA. We mapped the microtubule-binding region of Smc5 and generated a mutant with impaired microtubule binding activity. This mutant is viable in yeast but exhibited a cold-specific conditional lethality associated with mitotic arrest, aberrant spindle structures, and chromosome segregation defects. In an in vitro reconstitution assay, this Smc5 mutant also showed a compromised ability to protect microtubules from cold-induced depolymerization. Collectively, these findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity. 相似文献
3.
Maxime Lenormand Guillaume Papuga Olivier Argagnon Maxence Soubeyrand Guilhem De Barros Samuel Alleaume Sandra Luque 《Ecology and evolution》2019,9(1):237-250
The delimitation of bioregions helps to understand historical and ecological drivers of species distribution. In this work, we performed a network analysis of the spatial distribution patterns of plants in south of France (Languedoc‐Roussillon and Provence‐Alpes‐Côte d'Azur) to analyze the biogeographical structure of the French Mediterranean flora at different scales. We used a network approach to identify and characterize biogeographical regions, based on a large database containing 2.5 million of geolocalized plant records corresponding to more than 3,500 plant species. This methodology is performed following five steps, from the biogeographical bipartite network construction to the identification of biogeographical regions under the form of spatial network communities, the analysis of their interactions, and the identification of clusters of plant species based on the species contribution to the biogeographical regions. First, we identified two sub‐networks that distinguish Mediterranean and temperate biota. Then, we separated eight statistically significant bioregions that present a complex spatial structure. Some of them are spatially well delimited and match with particular geological entities. On the other hand, fuzzy transitions arise between adjacent bioregions that share a common geological setting, but are spread along a climatic gradient. The proposed network approach illustrates the biogeographical structure of the flora in southern France and provides precise insights into the relationships between bioregions. This approach sheds light on ecological drivers shaping the distribution of Mediterranean biota: The interplay between a climatic gradient and geological substrate shapes biodiversity patterns. Finally, this work exemplifies why fragmented distributions are common in the Mediterranean region, isolating groups of species that share a similar eco‐evolutionary history. 相似文献
4.
5.
Christine Delsarte Guillaume Etuin Laurent Petit 《Bioorganic & medicinal chemistry》2018,26(4):984-988
An improved process for the preparation of 1-methylcyclopropanol using the Kulinkovich reaction is described. The use of titanium tetramethoxide as catalyst resulted in minimal side product formation. The reaction, isolation and purification procedures were optimized so they can be easily implemented in multi-purpose equipment. 相似文献
6.
7.
Summary Fertility parameters were estimated inVaccinium myrtillus andV. vitis-idaea after self- and cross-pollinations performed in growth chamber. We showed a drastic decrease in fertility after self-pollination as compared to cross-pollination. Number of plump seeds per berry was compared with previous field data. In both species, growth room conditions improved plump seed number after cross-pollination but not after self-pollination. In addition, in order to enhance resources supply to young developing fruits, cytokinin application was tested inV. myrtillus but no effect was detected. We hypothesize that the partial self-sterility is due to inbreeding depression based on the expression of recessive lethals. 相似文献
8.
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
9.
The preceding paper (Bec, G., Kerjan, P., Zha, X.D., and Waller, J.P. (1989) J. Biol. Chem. 264, 21131-21137) described the purification to apparent homogeneity from rabbit liver, of a heterotypic complex comprising valyl-tRNA synthetase and Elongation Factor 1H. In the present study, valyl-tRNA synthetase was dissociated and separated from the other components of this complex by hydroxylapatite chromatography in the presence of 0.5 M NaSCN. The properties of the homogeneous mammalian enzyme were compared to those of the corresponding enzyme from yeast. Both behaved as monomeric entities, with apparent molecular masses of 140 and 125 kDa, respectively. Furthermore, both displayed strong affinity toward the polyanionic support heparin-Ultrogel, a property not manifested by the corresponding prokaryotic enzyme. However, unlike the yeast enzyme, that of mammalian origin additionally exhibited hydrophobic properties, as reflected by its affinity toward phenyl-Sepharose. A structural model is proposed according to which mammalian valyl-tRNA synthetase has conserved the polycationic N-terminal domain that distinguishes the corresponding lower eukaryotic enzyme from its prokaryotic counterpart, while acquiring a hydrophobic domain most likely responsible for its association to Elongation Factor 1H. 相似文献
10.