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101.
Sebastian M. Marcuccio Bryan C. Elmes George Holan E. John Middleton 《Nucleosides, nucleotides & nucleic acids》2013,32(10):1695-1701
Abstract An economical two pot synthesis of 2′,3′-dideoxycytidine (2) from N4-acetyl-cytidine (4) has been developed. The key feature of this sequence is the in situ reductive elimination of a mixture of 1-(3-bromo-3-deoxy-2,5-di-O-acetyl-β-D-xylofuranosyl)-N4-acetylcytosine (5) and 1-(2-bromo-3-deoxy-3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4-acetylcytosine (6) and subsequent hydrogenation of the resultant olefin over palladised charcoal. 相似文献
102.
Bryan Colin Nicholas Morgan Jones Claire Simons Hisao Nishimura Jiri Zemlicka 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):431-434
Abstract Anti-HIV agent (±)-cytallene (1b + 2b) was resolved by enantioselective acylation of (±)-N4-benzoylcytallene (1d + 2d) with vinyl butyrate in tetrahydrofuran catalyzed by lipase AK from Pseudomonas sp. and subsequent deacylation of 4d and 1d with ammonia in methanol. Optically pure enantiomers 1b and 2b were obtained. 相似文献
103.
Ken Okamoto Bryan T. Eger Tomoko Nishino Emil F. Pai Takeshi Nishino 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):888-893
Inhibitors of xanthine oxidoreductase block conversion of xanthine to uric acid and are therefore potentially useful for treatment of hyperuricemia or gout. We determined the crystal structure of reduced bovine milk xanthine oxidoreductase complexed with oxipurinol at 2.0 Å resolution. Clear electron density was observed between the N2 nitrogen of oxipurinol and the molybdenum atom of the molybdopterin cofactor, indicating that oxipurinol coordinated directly to molybdenum. Oxipurinol forms hydrogen bonds with glutamate802, arginine880, and glutamate1261, which have previously been shown to be essential for the enzyme reaction. We discuss possible differences in the hypouricemic effect of inhibitors, including allopurinol and newly developed inhibitors, based on their mode of binding in the crystal structures. 相似文献
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Leonel Lopez-Toledo Yazmin Portillo-Cruz María T. Pulido Bryan A. Endress 《Plant Ecology》2013,214(9):1115-1125
Seed dynamics are an important part of the life history of plants and may have strong implications on abundance and spatial distribution of populations. In this study, we explored how seed dynamics (removal, predation, germination) interact with micro-environmental conditions to affect the spatial structure of populations of Brahea aculeata (Arecaceae) in a tropical dry forest. B. aculeata is distributed throughout arroyo basins and attains its highest densities near to arroyos/rivers. We hypothesized that: (i) seed removal, predation and germination vary across topographic positions resulting in greater palm abundances adjacent to arroyos and (ii) seed removers/predators respond to both a seed density-dependent effect and a microclimate effect. To test this, in six arroyos basins, seeds were sown across three topographic positions (stream, mid and top of basins) with two seed abundances (1 and 10), protected and non-protected from potential predators. Predation, removal and germination were then followed. After 107 days, 100 % of the exposed seeds were removed/predated and none germinated. For seed removal, we found differences among topographic positions and seed densities with higher removal (up to 80 %) and lower predation rates for grouped seeds. Germination was only observed for protected seeds with higher germination rates in single (17 % ± 9) than in grouped seeds (4 % ± 1). The highest germination and establishment rates were adjacent to the streams; areas which had the lowest light intensity (mean ± SE = 883 ± 160 lm/ft2) and temperatures (mean ± SE = 20.1 ± 0.6 °C), and highest humidity (mean ± SE = 50.8 ± 1.8 %), especially during the rainy season. Differential seedling establishment rates across the landscape due to spatial patterns of seed predation/removal as well as micro-environmental variables appear to have implications for shaping the spatial structure of B. aculeata population at Sierra de Álamos, Mexico. 相似文献
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108.
Bhavna Bhasin Bryan Lau Mohamed G. Atta Derek M. Fine Michelle M. Estrella George J. Schwartz Gregory M. Lucas 《PloS one》2013,8(12)
Background
Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.Methods
We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.Results
The median mGFR was >100 ml/min/1.73 m2 in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.Conclusions
The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population. 相似文献109.
110.
Jordan R. Willis Bryan S. Briney Samuel L. DeLuca James E. Crowe Jr Jens Meiler 《PLoS computational biology》2013,9(4)
Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding. 相似文献