全文获取类型
收费全文 | 653篇 |
免费 | 66篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 13篇 |
2015年 | 28篇 |
2014年 | 42篇 |
2013年 | 41篇 |
2012年 | 45篇 |
2011年 | 40篇 |
2010年 | 37篇 |
2009年 | 21篇 |
2008年 | 33篇 |
2007年 | 25篇 |
2006年 | 29篇 |
2005年 | 23篇 |
2004年 | 23篇 |
2003年 | 26篇 |
2002年 | 23篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 16篇 |
1998年 | 11篇 |
1997年 | 14篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 14篇 |
1991年 | 4篇 |
1989年 | 9篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 9篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1954年 | 1篇 |
排序方式: 共有719条查询结果,搜索用时 125 毫秒
61.
Genetic interactions between farmed and wild conspecifics are of special concern in fisheries where large numbers of domesticated individuals are released into the wild. In the Atlantic salmon (Salmo salar), selective breeding since the 1970's has resulted in rapid genetic changes in commercially important traits, such as a doubling of the growth rate. Each year, farmed salmon escape from net pens, enter rivers, and interbreed with wild salmon. Field experiments demonstrate that genetic introgression may weaken the viability of recipient populations. However, due to the lack of diagnostic genetic markers, little is known about actual rates of gene flow from farmed to wild populations. Here we present a panel of 60 single nucleotide polymorphisms (SNPs) that collectively are diagnostic in identifying individual salmon as being farmed or wild, regardless of their populations of origin. These were sourced from a pool of 7000 SNPs comparing historical wild and farmed salmon populations, and were distributed on all but two of the 29 chromosomes. We suggest that the generic differences between farmed and wild salmon at these SNPs have arisen due to domestication. The identified panel of SNPs will permit quantification of gene flow from farmed to wild salmon populations, elucidating one of the most controversial potential impacts of aquaculture. With increasing global interest in aquaculture and increasing pressure on wild populations, results from our study have implications for a wide range of species. 相似文献
62.
Lazaro E Tram LT Bellecave P Guidicelli GL Anies G Thu HH Debelleix MP Vray M Recordon-Pinson P Taupin JL Lien TT Fleury H 《PloS one》2011,6(10):e26244
Background
To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding.Methods
We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score).Results
All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9) versus 2 (±0.7) in non-divergent ones (p<0.0001).Conclusions
Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area. 相似文献63.
Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals 总被引:23,自引:0,他引:23 下载免费PDF全文
Maines TR Lu XH Erb SM Edwards L Guarner J Greer PW Nguyen DC Szretter KJ Chen LM Thawatsupha P Chittaganpitch M Waicharoen S Nguyen DT Nguyen T Nguyen HH Kim JH Hoang LT Kang C Phuong LS Lim W Zaki S Donis RO Cox NJ Katz JM Tumpey TM 《Journal of virology》2005,79(18):11788-11800
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret. 相似文献
64.
Two plasmid DNA constructs were obtained by cloning separately into the eukaryotic expression vector pcDNA3.1/V5-His-TOPO the wall-associated protein A (wapA) gene of Streptococcus mutans GS-5 or its truncated derivative antigen A (agA) gene encoding a known candidate antigen for dental caries vaccine. The immunogenicity of the two constructs, designated pcDNA-wapA and pcDNA-agA, was compared by intranasal immunization of two groups of mice using the cationic DMRIE-C (1,2-dimyristyloxypropyl-3-dimethylhydroxy ethyl ammonium bromide-cholesterol) as an adjuvant. Immunization with pcDNA-wapA or pcDNA- agA resulted in specific salivary IgA and systemic IgG antibodies to the target antigens after two doses given at 3-week intervals. Higher salivary IgA level was observed in the mice immunized with the pcDNA-wapA vaccine compared to those immunized with the pcDNA-agA vaccine. Furthermore, anti-WapA antibody inhibited S. mutans sucrose-dependent adherence suggesting a potential protection against S. mutans colonization of the tooth, while anti-AgA had no significant effect. Indeed, prediction and analysis of protein epitopes showed that WapA contains highly promiscuous MHC-II binding motifs in addition to those found in AgA. Immunodot assay confirmed that WapA bound biotin-labeled dextran, whereas AgA did not. These data indicated that full-length WapA is a better candidate vaccine antigen than the soluble AgA, which is truncated in the hydrophobic membrane and wall-spanning region. 相似文献
65.
Temporal Changes between Ecological Regimes in a Range of Primary and Secondary Salinised Wetlands 总被引:4,自引:4,他引:0
Karin?Strehlow Jenny?DavisEmail author Lien?Sim Jane?Chambers Stuart?Halse David?Hamilton Pierre?Horwitz Arthur?McComb Ray?Froend 《Hydrobiologia》2005,552(1):17-31
Many rivers and wetlands in south-western Australia are threatened by salinisation due to rising saline watertables, which
have resulted from land clearing and the replacement of deep-rooted perennial species with shallow-rooted annual species.
A four to six weekly sampling program of water quality, submerged macrophytes and macroinvertebrates was undertaken at six
wetlands, from September 2002 to February 2004, to investigate seasonal variation in a range of primary and secondary saline
systems. The wetlands dried and filled at different times in response to local rainfall patterns, and salinities varied accordingly
with evapoconcentration and dilution. Two types of clear-water wetlands were recognised; those dominated by submerged aquatic
macrophytes (Ruppia, Lepilaena and Lamprothamnium) and those dominated by benthic microbial communities. Two types of turbid wetlands were also recognised; those with high
concentrations of phytoplankton and those with high concentrations of suspended sediments. A primary saline lake and two lakes
that have only recently been affected by secondary salinisation persisted in a clear, macrophyte-dominated regime throughout
most of the study period, except during drying and filling. Two lakes with a long history of secondary salinisation (70 years)
moved between regimes over the study period. A clear, benthic microbial community – dominated regime only persisted at the
wetland which contained permanent water throughout the study period. The turbid regimes were only present during drying and
refilling phases. A richer and more abundant macroinvertebrate fauna was associated with the clear, macrophyte- dominated
wetlands. Our results suggest that the development of management guidelines that recognise the presence of different ecological
regimes and that consider the interactions between water regime, salinity, and primary and secondary production will be more
useful in protecting biodiversity and ecological function in these systems than managing salinity as a single factor. 相似文献
66.
67.
68.
69.
70.
Gene expression analysis of zebrafish heart regeneration 总被引:1,自引:0,他引:1