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991.
992.
Zhang Z Ren Q Yang H Conrad MN Guacci V Kateneva A Dresser ME 《Molecular microbiology》2005,56(3):670-680
Budding yeast PDS5 is an essential gene in mitosis and is required for chromosome condensation and sister chromatid cohesion. Here we report that PDS also is required in meiosis. Pds5p localizes on chromosomes at all stages during meiotic cycle, except anaphase I. PDS5 plays an important role at first meiotic prophase. Failure in function of PDS5 causes premature separation of chromosomes. The loading of Pds5p onto chromosome requires the function of REC8, but the association of Rec8p with chromosome is independent of PDS5. Mutant analysis and live cell imaging indicate that PDS5 play a role in meiosis II as well. 相似文献
993.
Although gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) have independently been reported to suppress growth of cancer cells, their relative potencies are unknown. To determine the possible attenuating efficacies of dietary GLA or EPA on prostate carcinogenesis, we hereby report the in vitro effects of GLA, EPA and their 15-lipoxygenase (15-LOX) metabolites: 15(S)-HETrE and 15(S)-HEPE, respectively, on growth and arachidonic acid (AA) metabolism in human androgen-dependent (LNCaP) and androgen-independent (PC-3) prostatic cancer cells in culture. Specifically, both cells were preincubated respectively with the above PUFAs. Growth was determined by [3H]thymidine uptake and AA metabolism by HPLC analysis of the extracted metabolites. Our data revealed increased biosynthesis of prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5(S)-HETE) by both cells. Preincubation of the cells with 15(S)-HETrE or 15(S)-HEPE more markedly inhibited cellular growth and AA metabolism when compared to precursor PUFAs. Notably, 15(S)-HETrE exerted the greatest inhibitory effects. These findings therefore imply that dietary GLA rather than EPA should better attenuate prostate carcinogenesis via its in vivo generation of 15(S)-HETrE, thus warranting exploration. 相似文献
994.
Small reducing and linear oligo-beta-(1,3)-glucans, which are able to act as phytoallexin elicitors or as immunostimulating agents in anticancer therapy, were synthesized according to an iterative strategy that involved a unique key monosaccharidic donor. To avoid anomeric mixtures, the reducing entity of the target oligomers was first locked with benzyl alcohol and further selective deprotection of the 3-OH with DDQ afforded the desired building block as an acceptor. The latter was then used in a second cycle of glycosylation/deprotection to afford the desired disaccharide, and successive reiterations of this process provided the desired oligomers. Unusual conformational behaviors were observed by standard NMR sequences and supported by NOESY studies. Finally, removal of protecting groups afforded free tri-, tetra-, and pentaglucosides in good overall yields. Two oligosaccharides representing linear laminaritetraose and laminaripentaose were compared to the recently described beta-(1,3)-glucan phycarine. Following an intraperitoneal injection, the influx of monocytes and granulocytes into the blood and macrophages into the peritoneal cavity was comparable to that caused by phycarine. Similarly, both oligosaccharides stimulated phagocytic activity of granulocytes and macrophages. Using ELISA, we also demonstrated a significant stimulation of secretion of IL-1beta. Together these results suggest that the synthetic oligosaccharides have similar stimulatory effects as natural beta-(1,3)-glucans. 相似文献
995.
Manuel B.?MoralesEmail author Vincent?Bretagnolle Beatriz?Arroyo 《Biodiversity and Conservation》2005,14(13):3135-3150
Stochastic computer simulations are used to evaluate the sensitivity of Little bustard population parameters, estimating the
survival probabilities of the seven endangered Little bustard populations of central-western France for which conservation
actions are currentlybeing or have been implemented. Different scenarios of parameter compensation for those nuclei to establish
parameter levels assuring population viability are discussed. Adult survival, productivity per female, initial population
size and carrying capacity were the most sensitive parameters in a hypothetical, isolated population. Juvenile survival also
affected population survival, although its sensitivity was lower. Sex ratio did not have a linear effect on population survival,
but probability of extinction increased for extreme values. Productivity per female and initial population size, varied strongly
among the populations studied, determining their average time of extinction and growth rate. When a metapopulation scenario
was simulated, the survival probabilities of each population and the metapopulations stayed close to 1.0 if no mortality was
associated to migration. When mortality during migration was included in the simulations, the metapopulation's probability
of survival significantly decreased under 90%. This approach may help managers to correctly address conservation measures
and design effective strategies, which should be directed mainly to improve productivity, enhance female survival, and minimise
mortality during migration (e.g. promoting insect-rich nesting substrates, avoiding female killing and nest destruction at
harvesting, reducing the risk of collision with powerlines, or controlling poaching). 相似文献
996.
Zhao C Sham HL Sun M Stoll VS Stewart KD Lin S Mo H Vasavanonda S Saldivar A Park C McDonald EJ Marsh KC Klein LL Kempf DJ Norbeck DW 《Bioorganic & medicinal chemistry letters》2005,15(24):7604-5503
As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P1′ ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains. 相似文献
997.
Zask A Kaplan J Du X MacEwan G Sandanayaka V Eudy N Levin J Jin G Xu J Cummons T Barone D Ayral-Kaloustian S Skotnicki J 《Bioorganic & medicinal chemistry letters》2005,15(6):1641-1645
Potent and selective TACE and MMP inhibitors utilizing the diazepine and thiazepine ring systems were synthesized and evaluated for biological activity in in vitro and in vivo models of TNF-alpha release. Oral activity in the mouse LPS model of TNF-alpha release was seen. Efficacy in the mouse collagen induced arthritis model was achieved with diazepine 20. 相似文献
998.
Li Q Woods KW Wang W Lin NH Claiborne A Gu WZ Cohen J Stoll VS Hutchins C Frost D Rosenberg SH Sham HL 《Bioorganic & medicinal chemistry letters》2005,15(8):2033-2039
Beginning with the structure of tipifarnib (1), a series of inhibitors of FTase have been synthesized by transposition of the D-ring to the imidazole and subsequent modification of the 2-quinolone motif. The compounds in the new series may be achiral and have structural features that allow for analogs that are difficult or impossible to make in the tertiary carbon-based tipifarnib series. The most potent compound (4d) is 4 times more active in vitro against FTase than tipifarnib. 相似文献
999.
Romagnoli R Baraldi PG Jung MK Iaconinoto MA Carrion MD Remusat V Preti D Tabrizi MA Francesca F De Clercq E Balzarini J Hamel E 《Bioorganic & medicinal chemistry letters》2005,15(18):4048-4052
A new series of compounds, in which the 2-amino-4-methoxyphenyl ring of phenstatin analogue 5 was replaced with 2- or 3-amino-benzoheterocycles, was synthesized and evaluated for antiproliferative activity and inhibition of colchicine binding. The lack of activity of 3',4'-dimethoxy- and 4'-methoxy-benzoyl derivatives (8 and 9, respectively) indicates that the 3',4',5'-trimethoxybenzoyl moiety is critical for the activity. Two compounds, 7 and 11, displayed potent antiproliferative activity, with IC50 values ranging from 25 to 100 nM against a variety of cancer cell lines. Derivative 11 was more active than CA-4 as an inhibitor of tubulin polymerization. The results demonstrated that the antiproliferative activity was correlated with inhibition of tubulin polymerization. 相似文献
1000.
Wang GT Wang S Gentles R Sowin T Maring CJ Kempf DJ Kati WM Stoll V Stewart KD Laver G 《Bioorganic & medicinal chemistry letters》2005,15(1):125-128
(+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM. 相似文献