首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   648篇
  免费   14篇
  662篇
  2024年   5篇
  2023年   7篇
  2022年   7篇
  2021年   21篇
  2020年   14篇
  2019年   17篇
  2018年   18篇
  2017年   11篇
  2016年   20篇
  2015年   32篇
  2014年   39篇
  2013年   43篇
  2012年   59篇
  2011年   45篇
  2010年   29篇
  2009年   19篇
  2008年   26篇
  2007年   41篇
  2006年   30篇
  2005年   31篇
  2004年   31篇
  2003年   19篇
  2002年   17篇
  2001年   4篇
  2000年   5篇
  1999年   4篇
  1998年   11篇
  1997年   3篇
  1995年   2篇
  1994年   2篇
  1993年   2篇
  1992年   4篇
  1991年   2篇
  1990年   1篇
  1989年   3篇
  1988年   2篇
  1987年   1篇
  1986年   3篇
  1985年   2篇
  1984年   3篇
  1983年   2篇
  1982年   4篇
  1981年   2篇
  1980年   3篇
  1978年   4篇
  1976年   1篇
  1975年   2篇
  1973年   2篇
  1972年   2篇
  1970年   4篇
排序方式: 共有662条查询结果,搜索用时 0 毫秒
1.
    
Through targeted inactivation of the ssrA and smpB genes, we establish that the trans-translation process is necessary for normal growth, adaptation to cellular stress and virulence by the bacterial pathogen Francisella tularensis. The mutant bacteria grow slower, have reduced resistance to heat and cold shocks, and are more sensitive to oxidative stress and sublethal concentrations of antibiotics. Modifications of the tmRNA tag and use of higher-resolution mass spectrometry approaches enabled the identification of a large number of native tmRNA substrates. Of particular significance to understanding the mechanism of trans-translation, we report the discovery of an extended tmRNA tag and extensive ladder-like pattern of endogenous protein-tagging events in F. tularensis that are likely to be a universal feature of tmRNA activity in eubacteria. Furthermore, the structural integrity and the proteolytic function of the tmRNA tag are both crucial for normal growth and virulence of F. tularensis. Significantly, trans-translation mutants of F. tularensis are impaired in replication within macrophages and are avirulent in mouse models of tularemia. By exploiting these attenuated phenotypes, we find that the mutant strains provide effective immune protection in mice against lethal intradermal, intraperitoneal and intranasal challenges with the fully virulent parental strain.  相似文献   
2.
Journal of Plant Growth Regulation - Auxin is a hormone that delays ripening in part by reducing anthocyanin content and impairing color development. Auxin content declines during the ripening...  相似文献   
3.

Background

The bovine rumen maintains a diverse microbial community that serves to break down indigestible plant substrates. However, those bacteria specifically adapted to degrade cellulose, the major structural component of plant biomass, represent a fraction of the rumen microbiome. Previously, we proposed scaC as a candidate for phylotyping Ruminococcus flavefaciens, one of three major cellulolytic bacterial species isolated from the rumen. In the present report we examine the dynamics and diversity of scaC-types both within and between cattle temporally, following a dietary switch from corn-silage to grass-legume hay. These results were placed in the context of the overall bacterial population dynamics measured using the 16S rRNA.

Principal Findings

As many as 117 scaC-types were estimated, although just nineteen were detected in each of three rumens tested, and these collectively accounted for the majority of all types present. Variation in scaC populations was observed between cattle, between planktonic and fiber-associated fractions and temporally over the six-week survey, and appeared related to scaC phylogeny. However, by the sixth week no significant separation of scaC populations was seen between animals, suggesting enrichment of a constrained set of scaC-types. Comparing the amino-acid translation of each scaC-type revealed sequence variation within part of the predicted dockerin module but strong conservation in the N-terminus, where the cohesin module is located.

Conclusions

The R. flavefaciens species comprises a multiplicity of scaC-types in-vivo. Enrichment of particular scaC-types temporally, following a dietary switch, and between fractions along with the phylogenetic congruence suggests that functional differences exist between types. Observed differences in dockerin modules suggest at least part of the functional heterogeneity may be conferred by scaC. The polymorphic nature of scaC enables the relative distribution of R. flavefaciens strains to be examined and represents a gene-centric approach to investigating the intraspecific adaptation of an important specialist population.  相似文献   
4.
5.
    
Year-round continuous reproduction in tropical regions is an established paradigm in marine ecology. In this study, we tested this paradigm using the ghost shrimp Callichirus seilacheri from the tropical eastern Pacific as a model species. We also examined size-frequency distribution, sex ratio, and recruitment cycle to contribute to the biological knowledge of this species. To this end, a total of 456 individuals of C. seilacheri were collected during 12 months of sampling. Population structure was symmetrical for both sexes, and the overall sex ratio did not differ from evenness. Males outnumbered females in smaller size classes, though, revealing a potential sex-dependent mortality in small individuals. The breeding pattern followed the well-marked seasonal regime of the region, with ovigerous females registered during the rainy season. While natural variation in the seawater temperature had no influence on reproduction of this species, changes in water salinity possibly triggered the appearance of egg-bearing females in the population. Recruitment occurred throughout the year but was more intense during the dry season, following the appearance of ovigerous females. The adaptability of the life cycle of C. seilacheri to the seasonal climate provides further evidence that reproduction in tropical species is not always continuous.  相似文献   
6.
Excitatory synaptic transmission is largely mediated by AMPA receptors (AMPARs) present at the postsynaptic density. Recent studies in single molecule tracking of AMPAR has revealed that extrasynaptic AMPARs are highly mobile and thus might serve as a readily available pool for their synaptic recruitment during synaptic plasticity events such as long-term potentiation (LTP). Because this hypothesis relies on the cell's ability to increase the number of diffusional traps or 'slots' at synapses during LTP, we will review a number of protein-protein interactions that might impact AMPARs lateral diffusion and thus potentially serve as slots. Recent studies have identified the interaction between the AMPAR-Stargazin complex and PSD-95 as the minimal components of the diffusional trapping slot. We will overview the molecular basis of this critical interaction, its activity-dependent regulation and its potential contribution to LTP.  相似文献   
7.
8.
In an attempt to design new antitumoral drugs based on transplatin complexes, we determined the experimental conditions for the preparation of trans-[Pt((CH(3))(2)CNOH)((CH(3))(2)CHNH(2))Cl(2)], and solved the crystal structure. The cytotoxicity of the novel complex, the cis counterpart, cisplatin, and a trans complex with aliphatic amines, as well as the capacity of some of these complexes to cause either apoptotic or necrotic cell death, was comparatively examined in NRK-52E rat renal tubular cells and HepG2 human hepatoma cells. The results indicate that the oxime complex with trans geometry, but not the one with cis geometry, causes death by apoptosis, making the complex potentially suitable for therapeutic purposes. However cytotoxicity values are higher in the case of cis geometry than in trans geometry in both tumoral and non-tumoral cell lines.  相似文献   
9.
Yellow anacondas (Eunectes notaeus) are large, semiaquatic boid snakes found in wetland systems in South America. These snakes are commercially harvested under a sustainable management plan in Argentina, so information regarding population structuring can be helpful for determination of management units. We evaluated genetic structure and migration using partial sequences from the mitochondrial control region and mitochondrial genes cyt-b and ND4 for 183 samples collected within northern Argentina. A group of landscape features and environmental variables including several treatments of temperature and precipitation were explored as potential drivers of observed genetic patterns. We found significant population structure between most putative population comparisons and bidirectional but asymmetric migration in several cases. The configuration of rivers and wetlands was found to be significantly associated with yellow anaconda population structure (IBD), and important for gene flow, although genetic distances were not significantly correlated with the environmental variables used here. More in-depth analyses of environmental data may be needed to fully understand the importance of environmental conditions on population structure and migration. These analyses indicate that our putative populations are demographically distinct and should be treated as such in Argentina's management plan for the harvesting of yellow anacondas.  相似文献   
10.
Herein, we report the biochemical and functional characterization of a novel Ca(2+)-activated nucleoside diphosphatase (apyrase), CApy, of the intracellular gut pathogen Cryptosporidium. The purified recombinant CApy protein displayed activity, substrate specificity and calcium dependency strikingly similar to the previously described human apyrase, SCAN-1 (soluble calcium-activated nucleotidase 1). CApy was found to be expressed in both Cryptosporidium parvum oocysts and sporozoites, and displayed a polar localization in the latter, suggesting a possible co-localization with the apical complex of the parasite. In vitro binding experiments revealed that CApy interacts with the host cell in a dose-dependent fashion, implying the presence of an interacting partner on the surface of the host cell. Antibodies directed against CApy block Cryptosporidium parvum sporozoite invasion of HCT-8 cells, suggesting that CApy may play an active role during the early stages of parasite invasion. Sequence analyses revealed that the capy gene shares a high degree of homology with apyrases identified in other organisms, including parasites, insects and humans. Phylogenetic analysis argues that the capy gene is most likely an ancestral feature that has been lost from most apicomplexan genomes except Cryptosporidium, Neospora and Toxoplasma.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号