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91.
Salvador Casares Eiso AB Henk Eshuis Obdulio Lopez-Mayorga Nico AJ van Nuland Francisco Conejero-Lara 《BMC structural biology》2007,7(1):22
Background
SH3 domains are small protein modules of 60–85 amino acids that bind to short proline-rich sequences with moderate-to-low affinity and specificity. Interactions with SH3 domains play a crucial role in regulation of many cellular processes (some are related to cancer and AIDS) and have thus been interesting targets in drug design. The decapeptide APSYSPPPPP (p41) binds with relatively high affinity to the SH3 domain of the Abl tyrosine kinase (Abl-SH3), while it has a 100 times lower affinity for the α-spectrin SH3 domain (Spc-SH3). 相似文献92.
HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community
van Tienen C Schim van der Loeff M Peterson I Cotten M Andersson S Holmgren B Vincent T de Silva T Rowland-Jones S Aaby P Whittle H 《PloS one》2011,6(12):e29026
Background
Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau.Methods
In 1990, 1997 and 2007, adult residents (aged ≥15 years) were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR), comparing retrovirus-infected versus uninfected people.Results
A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0–20.3). The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9) for HIV-1, 4.1 (3.4–5.0) for HIV-2, 3.6 (2.9–4.6) for HTLV-1, and 1.6 (1.5–1.8) for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years) to 12.7 in the youngest (15–29 years). The HR for HIV-2 infection varied from 1.2 (oldest) to 9.1 (youngest), and for HTLV-1 infection from 1.2 (oldest) to 3.8 (youngest).Conclusions
HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people. 相似文献93.
M J Whittle 《BMJ (Clinical research ed.)》1976,2(6039):795-796
94.
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96.
Whittle CA 《Journal of evolutionary biology》2006,19(1):302-308
One of the main goals of molecular evolutionary biology is to determine the factors that influence the evolutionary rate of selectively neutral DNA, but much remains unknown, especially for plants. Key factors that could alter the mutation rate include environmental tolerances (because they reflect a plants vulnerability to changes in habitat), the pollen:ovule ratio (as it is associated with the number of mitotic divisions) and seed longevity (because this influences the number of generations per unit time in plants). This is the first study to demonstrate that seed bank persistence and drought tolerance are positively associated with molecular evolutionary rates in plants and that pollen:ovule ratio, shade tolerance and salinity tolerance have no detectable relationship. The implications of the findings to our understanding of the impact of environmental agents, the number of cell divisions and cell aging on neutral DNA sequence evolution are discussed. 相似文献
97.
Georgina Caruana Peter G. Farlie Adam H. Hart Stefan Bagheri-Fam Megan J. Wallace Michael S. Dobbie Christopher T. Gordon Kerry A. Miller Belinda Whittle Helen E. Abud Ruth M. Arkell Timothy J. Cole Vincent R. Harley Ian M. Smyth John F. Bertram 《PloS one》2013,8(3)
Background
Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking gene function to normal development and human disorders. To generate mouse models harbouring novel alleles that are involved in organogenesis we conducted a phenotype-driven, genome-wide mutagenesis screen in mice using the mutagen N-ethyl-N-nitrosourea (ENU).Methodology/Principal Findings
ENU was injected into male C57BL/6 mice and the mutations transmitted through the germ-line. ENU-induced mutations were bred to homozygosity and G3 embryos screened at embryonic day (E) 13.5 and E18.5 for abnormalities in limb and craniofacial structures, skin, blood, vasculature, lungs, gut, kidneys, ureters and gonads. From 52 pedigrees screened 15 were detected with anomalies in one or more of the structures/organs screened. Using single nucleotide polymorphism (SNP)-based linkage analysis in conjunction with candidate gene or next-generation sequencing (NGS) we identified novel recessive alleles for Fras1, Ift140 and Lig1.Conclusions/Significance
In this study we have generated mouse models in which the anomalies closely mimic those seen in human disorders. The association between novel mutant alleles and phenotypes will lead to a better understanding of gene function in normal development and establish how their dysfunction causes human anomalies and disease. 相似文献98.
Lopes AR Jaye A Dorrell L Sabally S Alabi A Jones NA Flower DR De Groot A Newton P Lascar RM Williams I Whittle H Bertoletti A Borrow P Maini MK 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(1):307-316
Virus-specific CD8(+) T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8(+) T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8(+) T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8(+) T cells was associated with an enhanced potential for CD8 expansion and IFN-gamma production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8(+) T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8(+) T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes. 相似文献
99.
M. Lombroso S. Nicosia R. Paoletti B.J.R. Whittle S. Moncada J.R. Vane 《Prostaglandins & other lipid mediators》1984,27(2):321-333
Prostacyclin, (PGI2) is a potent but unstable inhibitor of platelet aggregation, probably acting through stimulation of adenylate cyclase.A stable analogue of prostacyclin with antiaggregatory properties, 5,6-dihydro-PGI2 (6β-PGI), and PGE1 can compete for the binding sites labelled by 3H-PGI2 in human platelet membranes (the affinity being PGI2 > PGE1 > 6β -PGI1). Both 6β-PGI1 and PGE1, as well as PGI2, bind to two classes of binding sites. 6β -PGI1 and PGE1 activate adenylate cyclase to the same extent as PGI2,with a rank order of potency which parallels that observed in binding experiments. The stimulation of this enzyme is brought about by interaction of each these prostanoids with two different classes of components. The comparison of binding and adenylate cyclase data suggests that the sites to which PGI2, 6β -PGI1 and PGE1 bind might be coupled to the activation of adenylate cyclase. Since 6β-PGI1 seems to act through the same molecular mechanisms as PGI2, because of its stability it is an useful tool to investigate the mode of action of prostacyclin in platelets. 相似文献
100.
Abstract: The conversion of γ-aminobutyrate (GABA) via succinic semialdehyde to γ-hydroxybutyrate has been examined in rat brain homogenates. A number of anticonvulsants, including sodium valproate and phenobarbitone, inhibited this metabolic pathway. These results are interpreted in the light of the characteristics of aldehyde reductases known to reduce succinic semialdehyde. 相似文献