全文获取类型
收费全文 | 2739篇 |
免费 | 178篇 |
专业分类
2917篇 |
出版年
2023年 | 15篇 |
2022年 | 39篇 |
2021年 | 69篇 |
2020年 | 58篇 |
2019年 | 57篇 |
2018年 | 47篇 |
2017年 | 54篇 |
2016年 | 92篇 |
2015年 | 135篇 |
2014年 | 162篇 |
2013年 | 203篇 |
2012年 | 264篇 |
2011年 | 252篇 |
2010年 | 145篇 |
2009年 | 109篇 |
2008年 | 195篇 |
2007年 | 156篇 |
2006年 | 142篇 |
2005年 | 138篇 |
2004年 | 115篇 |
2003年 | 101篇 |
2002年 | 78篇 |
2001年 | 17篇 |
2000年 | 12篇 |
1999年 | 21篇 |
1998年 | 22篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1984年 | 5篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1978年 | 6篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1973年 | 6篇 |
1968年 | 11篇 |
1966年 | 4篇 |
1965年 | 3篇 |
1964年 | 5篇 |
1962年 | 5篇 |
1957年 | 5篇 |
1955年 | 3篇 |
排序方式: 共有2917条查询结果,搜索用时 15 毫秒
171.
Hoffmann EH Malafronte RS Moraes-Avila SL Osakabe AL Wunderlich G Durham AM Ribolla PE del Portillo HA Ferreira MU 《Gene》2006,376(2):224-230
The recent evolution of Plasmodium falciparum is at odds with the extensive polymorphism found in most genes coding for antigens. Here, we examined the patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2), a major malarial repetitive surface antigen. We compared the msp-2 gene sequences from closely related clones derived from sympatric parasite isolates from Brazilian Amazonia and used microsatellite typing to examine, in these same clones, the haplotype background of chromosome 2, where msp-2 is located. We found examples of msp-2 sequence rearrangements putatively created by nonreciprocal recombinational events, such as replication slippage and gene conversion, while maintaining the chromosome haplotype. We conclude that these nonreciprocal recombination events may represent a major source of antigenic diversity in MSP-2 in P. falciparum populations with low rates of classical meiotic recombination. 相似文献
172.
Michael J. Garner Carolee Carson Erika J. Lingohr Aamir Fazil Victoria L. Edge Jan Trumble Waddell 《PloS one》2015,10(4)
Background
Antimicrobial resistance (AMR) of infectious agents is a growing concern for public health organizations. Given the complexity of this issue and how widespread the problem has become, resources are often insufficient to address all concerns, thus prioritization of AMR pathogens is essential for the optimal allocation of risk management attention. Since the epidemiology of AMR pathogens differs between countries, country-specific assessments are important for the determination of national priorities.Objective
To develop a systematic and transparent approach to AMR risk prioritization in Canada.Methods
Relevant AMR pathogens in Canada were selected through a transparent multi-step consensus process (n=32). Each pathogen was assessed using ten criteria: incidence, mortality, case-fatality, communicability, treatability, clinical impact, public/political attention, ten-year projection of incidence, economic impact, and preventability. For each pathogen, each criterion was assigned a numerical score of 0, 1, or 2, and multiplied by criteria-specific weighting determined through researcher consensus of importance. The scores for each AMR pathogen were summed and ranked by total score, where a higher score indicated greater importance. A sensitivity analysis was conducted to determine the effects of changing the criteria-specific weights.Results
The AMR pathogen with the highest total weighted score was extended spectrum B-lactamase-producing (ESBL) Enterobacteriaceae (score=77). When grouped by percentile, ESBL Enterobacteriaceae, Clostridium difficile, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus were in the 80-100th percentile.Conclusion
This assessment provides useful information for prioritising public health strategies regarding AMR resistance at the national level in Canada. As the AMR environment and challenges change over time and space, this systematic and transparent approach can be adapted for use by other stakeholders domestically and internationally. Given the complexity of influences, resource availability and multiple stakeholders, regular consideration of AMR activities in the public health realm is essential for appropriate and responsible prioritisation of risk management that optimises the health and security of the population. 相似文献173.
174.
Molecular characterization of ura1, a mutant allele for orotidine-5'-monophosphate decarboxylase in Schizophyllum commune 总被引:1,自引:0,他引:1
Abstract The basis of the auxotrophic ural phenotype in Schizophyllum commune has been investigated. Two point mutations causing changes in conserved amino acid positions 62 (from lysine to glutamate) and 79 (from leucine to phenylalanine) most likely are the cause for the observed phenotype, whereas the overall gene structure was unchanged. Since reversion rates in this locus are extremely low, a single point mutation could not be expected to be the cause for the mutation. Besides the two point mutations expected to be induced by UV mutagenesis, the two alleles investigated from independently isolated strains differ by approximately 7% in nucleic acid sequence and about 3% in amino acid sequence, indicating a distant relationship between the strains used. 相似文献
175.
Lessonia trabeculata is one of the major kelps found along the northern coast of Chile. In addition to its ecological and economic importance, L. trabeculata may be severely affected by environmental disturbances such as El Níño, which during 1982–1983 cleared wide areas along the coast of Peru and Chile. The main goal of this work was to mass culture L. trabeculata and to observe the growth of sporophytes obtained in the laboratory and cultured in the sea. Juvenile sporophytes obtained in the laboratory were attached between 1 and 6 m in depth. The linear growth rate, as blade elongation, was recorded weekly for seven months. No significant differences (p < 0.05) were found in sporophyte blade linear growth at different depths. The best elongation growth rate was 7.5 ± 1.6 mm d–1 at 3 m during March. This preliminary work suggests that L. trabeculata follows an annual growth cycle similar to that of other Laminariales with a high rate of blade elongation during the summer and decreasing towards autumn. This species can be considered a potential candidate for aquaculture to increase the availability of raw material and aid in repopulation of overexploited areas. 相似文献
176.
The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization 总被引:13,自引:0,他引:13 下载免费PDF全文
Several microtubule-binding proteins including EB1, dynactin, APC, and CLIP-170 localize to the plus-ends of growing microtubules. Although these proteins can bind to microtubules independently, evidence for interactions among them has led to the hypothesis of a plus-end complex. Here we clarify the interaction between EB1 and dynactin and show that EB1 binds directly to the N-terminus of the p150(Glued) subunit. One function of a plus-end complex may be to regulate microtubule dynamics. Overexpression of either EB1 or p150(Glued) in cultured cells bundles microtubules, suggesting that each may enhance microtubule stability. The morphology of these bundles, however, differs dramatically, indicating that EB1 and dynactin may act in different ways. Disruption of the dynactin complex augments the bundling effect of EB1, suggesting that dynactin may regulate the effect of EB1 on microtubules. In vitro assays were performed to elucidate the effects of EB1 and p150(Glued) on microtubule polymerization, and they show that p150(Glued) has a potent microtubule nucleation effect, whereas EB1 has a potent elongation effect. Overall microtubule dynamics may result from a balance between the individual effects of plus-end proteins. Differences in the expression and regulation of plus-end proteins in different cell types may underlie previously noted differences in microtubule dynamics. 相似文献
177.
Sphingosine-dependent protein kinase-1, directed to 14-3-3, is identified as the kinase domain of protein kinase C delta 总被引:2,自引:0,他引:2
Hamaguchi A Suzuki E Murayama K Fujimura T Hikita T Iwabuchi K Handa K Withers DA Masters SC Fu H Hakomori S 《The Journal of biological chemistry》2003,278(42):41557-41565
Some protein kinases are known to be activated by d-erythro-sphingosine (Sph) or N,N-dimethyl-d-erythro-sphingosine (DMS), but not by ceramide, Sph-1-P, other sphingolipids, or phospholipids. Among these, a specific protein kinase that phosphorylates Ser60, Ser59, or Ser58 of 14-3-3beta, 14-3-3eta, or 14-3-3zeta, respectively, was termed "sphingosine-dependent protein kinase-1" (SDK1) (Megidish, T., Cooper, J., Zhang, L., Fu, H., and Hakomori, S. (1998) J. Biol. Chem. 273, 21834-21845). We have now identified SDK1 as a protein having the C-terminal half kinase domain of protein kinase Cdelta (PKCdelta) based on the following observations. (i). Large-scale preparation and purification of proteins showing SDK1 activity from rat liver (by six steps of chromatography) gave a final fraction with an enhanced level of an approximately 40-kDa protein band. This fraction had SDK1 activity approximately 50000-fold higher than that in the initial extract. (ii). This protein had approximately 53% sequence identity to the Ser/Thr kinase domain of PKCdelta based on peptide mapping using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry data. (iii). A search for amino acid homology based on the BLAST algorithm indicated that the only protein with high homology to the approximately 40-kDa band is the kinase domain of PKCdelta. The kinase activity of PKCdelta did not depend on Sph or DMS; rather, it was inhibited by these sphingoid bases, i.e. PKCdelta did not display any SDK1 activity. However, strong SDK1 activity became detectable when PKCdelta was incubated with caspase-3, which releases the approximately 40-kDa kinase domain. PKCdelta and SDK1 showed different lipid requirements and substrate specificity, although both kinase activities were inhibited by common PKC inhibitors. The high susceptibility of SDK1 to Sph and DMS accounts for their important modulatory role in signal transduction. 相似文献
178.
Hamaguchi A Suzuki E Murayama K Fujimura T Hikita T Iwabuchi K Handa K Withers DA Masters SC Fu H Hakomori S 《Biochemical and biophysical research communications》2003,307(3):589-594
A specific protein kinase that phosphorylates Ser60, Ser59, or Ser58 of 14-3-3beta, eta, or zeta, respectively, only in the presence of sphingosine (Sph) or N,N-dimethyl-Sph (DMS), was termed "sphingosine-dependent protein kinase-1" (SDK1) [J. Biol. Chem. 273(34) (1998) 21834]. We have now identified SDK1 as a protein having the same amino acid sequence as in the C-terminal-half kinase domain of PKCdelta, with approximately 40 kDa molecular mass, based on large-scale purification of a protein from rat liver, and partial sequence using three different combinations of LC-MS or LC-MS/MS with respective search engine. PKCdelta did not display any SDK1 activity and PKCdelta activity was inhibited by Sph and DMS. However, strong SDK1 activity, only in the presence of Sph or DMS, became detectable when PKCdelta was incubated with caspase-3, which releases the approximately 40 kDa kinase domain. 相似文献
179.
180.