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991.
Cephalorhynchus commersonii is distributed in the nearshore coastal waters of South America, and thus is particularly vulnerable to bycatch in coastal nets and trawls. Our study documents genetic structure in presumed Commerson's dolphin subpopulations along the southern Argentina coastline, from the Ría Deseado in the north to Ría Gallegos in the south, and focuses on the potential for depletion in the apparently more heavily impacted Ría Gallegos area. Only two control region (423 bp) haplotypes were shared among all these locations (out of 11 identified), and striking differences in haplotype frequencies between areas are apparent. AMOVA analysis, using mitochondrial sequence data, indicates significant population subdivision (overall FST= 0.21, P < 0.001) between Ría Deseado (n= 8), Bahía San Julián (n= 11), Ría Gallegos (n= 31), and a small sample of dolphins from the captive colony at San Diego Seaworld (n= 7) derived from animals originally captured in the Strait of Magellan. Comparisons based on haplotypic distances indicated relatively strong differences between regions (ΦST= 0.30, P < 0.001). This research provides the first indication of reduced gene flow and genetic differentiation within local subpopulations of Commerson's dolphins, along a relatively small stretch of coastline. 相似文献
992.
Risso's dolphins (Grampus griseus) are widely distributed throughout temperate to tropical pelagic waters of the world and are one of the most frequently encountered cetaceans in eastern Taiwanese coastal waters. Because their life history is poorly known, the goal of this study was to investigate the relationship between age, body length, and sexual maturity of Risso's dolphins in Taiwanese waters. Ninety‐two carcasses of dead‐stranded or fisheries bycaught dolphins (1994–2008) were measured and dissected (total body length, TBL 125–290 cm); sexual maturity was assessed in 33 dolphins; and age was estimated by counting dentinal growth layer groups in routine histologically prepared tooth sections of 28 dolphins. Sexual dimorphism in TBL was not detected. The onset of sexual maturity occurred at 240–255 cm in females and 253–265 cm in males, which was at about 10 yr of age for both sexes. Our stranding, bycatch, and previous boat survey records suggest that Risso's dolphins occur year‐round and likely have a summer‐fall calving season in Taiwanese waters. The similar life history parameters and calving season in dolphins from Taiwanese and Japanese waters suggest a common population in the northwest Pacific, which has a noticeably shorter body length than in other regions. 相似文献
993.
YagE is a 33 kDa prophage protein encoded by CP4-6 prophage element in Escherichia coli K12 genome. Here, we report the structures of YagE complexes with pyruvate (PDB Id 3N2X) and KDGal (2-keto-3-deoxy galactonate) (PDB Id 3NEV) at 2.2A resolution. Pyruvate depletion assay in presence of glyceraldehyde shows that YagE catalyses the aldol condensation of pyruvate and glyceraldehyde. Our results indicate that the biochemical function of YagE is that of a 2-keto-3-deoxy gluconate (KDG) aldolase. Interestingly, E. coli K12 genome lacks an intrinsic KDG aldolase. Moreover, the over-expression of YagE increases cell viability in the presence of certain bactericidal antibiotics, indicating a putative biological role of YagE as a prophage encoded virulence factor enabling the survival of bacteria in the presence of certain antibiotics. The analysis implies a possible mechanism of antibiotic resistance conferred by the over-expression of prophage encoded YagE to E. coli. 相似文献
994.
Boy KM Guernon JM Shi J Toyn JH Meredith JE Barten DM Burton CR Albright CF Marcinkeviciene J Good AC Tebben AJ Muckelbauer JK Camac DM Lentz KA Bronson JJ Olson RE Macor JE Thompson LA 《Bioorganic & medicinal chemistry letters》2011,21(22):6916-6924
The synthesis, evaluation, and structure-activity relationships of a class of γ-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of γ-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented. 相似文献
995.
Chemical structure of fomitellan A, a polysaccharide with a mitogenic effect isolated from the fruiting bodies of Fomitella fraxinea, has been assigned as a mannofucogalactan with a repeating unit of penta-saccharide, which was composed of a (1→6)-linked d-galactopyranosyl backbone having a C-2 position substituted with disaccharide units of 3-O-d-mannopyranosyl-l-fucopyranosyl residue. The 1H and 13C NMR signals of fomitellan A have been completely assigned by extensive NMR experiments. 相似文献
996.
Based on the conjugate strategy, two neutral 99mTc labeled 2-(1-(6-(dialkylamino)naphthalen-2-yl)ethylidene)malononitrile (DDNP) and 1-(6-(dialkylamino)naphthalen-2-yl)ethanone (ENE) derivatives, and their corresponding rhenium complexes were synthesized. In vitro fluorescent staining indicated that the corresponding rhenium derivatives selectively stained the β-amyloid (Aβ) plaques in the brain sections of AD model mice with low background. Compared with FDDNP and FENE, the affinities of the corresponding rhenium derivatives to Aβ aggregates decreased about 10-14-fold. In vivo biodistribution experiments in normal mice showed that 99mTc-MAMA-ENE displayed medium initial brain uptake (0.65 %ID/g at 2 min) with a reasonable washout from the brain (0.19 %ID/g at 2 h) while 99mTc-MAMA-DDNP showed a low brain uptake (0.28 %ID/g at 2 min). Further optimize these 99mTc-labeled tracers in order to improve their binding affinities to Aβ plaques and diffusion through the blood brain barrier may generate useful imaging agents for SPECT. 相似文献
997.
Kumar TS Mishra S Deflorian F Yoo LS Phan K Kecskés M Szabo A Shinkre B Gao ZG Trenkle W Jacobson KA 《Bioorganic & medicinal chemistry letters》2011,21(9):2740-2745
Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A2A adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for 18F incorporation), and fluorophore reporter groups (e.g., BODIPY conjugate 14, Ki 15 nM). The potent and A2AAR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A2AAR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A2AAR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A2AAR. 相似文献
998.
Several QSAR (quantitative structure-activity relationships) models for predicting the inhibitory activity of 117 Aurora-A kinase inhibitors were developed. The whole dataset was split into a training set and a test set based on two different methods, (1) by a random selection; and (2) on the basis of a Kohonen’s self-organizing map (SOM). Then the inhibitory activity of 117 Aurora-A kinase inhibitors was predicted using multilinear regression (MLR) analysis and support vector machine (SVM) methods, respectively. For the two MLR models and the two SVM models, for the test sets, the correlation coefficients of over 0.92 were achieved. 相似文献
999.
Arbuckle W Baugh M Belshaw S Bennett DJ Bruin J Cai J Cameron KS Claxton C Dempster M Everett K Fradera X Hamilton W Jones PS Kinghorn E Long C Martin I Robinson J Westwood P 《Bioorganic & medicinal chemistry letters》2011,21(3):932-935
Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pka of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pka 6-8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen. 相似文献
1000.
Bolognesi ML Bartolini M Tarozzi A Morroni F Lizzi F Milelli A Minarini A Rosini M Hrelia P Andrisano V Melchiorre C 《Bioorganic & medicinal chemistry letters》2011,21(9):2655-2658
Memoquin (1) is a lead compound multitargeted against Alzheimer’s disease (AD). It is an AChE inhibitor, free-radical scavenger, and inhibitor of amyloid-β (Aβ) aggregation. A new series of 1 derivatives was designed and synthesized by linking its 2,5-diamino-benzoquinone core with motifs that are present in the structure of known amyloid binding agents like curcumin, the benzofuran derivative SKF64346, or the benzothiazole bearing compounds KHG21834 and BTA-1. The weaker AChE inhibitory potencies and the concomitant nearly equipotent anti-amyloid activities of the new compounds with respect to 1 resulted in a more balanced biological profile against both targets. Selected compounds turned out to be effective Aβ aggregation inhibitors in a cell-based assay. By properly combining two or more distinct pharmacological properties in a molecule, we can achieve greater effectiveness compared to single-targeted drugs for investigating AD. 相似文献