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91.
Ferraris D Ko YS Calvin D Chiou T Lautar S Thomas B Wozniak K Rojas C Kalish V Belyakov S 《Bioorganic & medicinal chemistry letters》2004,14(22):5579-5583
In this paper, the synthesis and structure-activity relationships (SAR) of two classes of electrophile-based dipeptidyl peptidase IV (DPP IV) inhibitors, the ketopyrrolidines and ketoazetidines, is discussed. The SAR of these series demonstrate that the 2-thiazole, 2-benzothiazole, and 2-pyridylketones are optimal S1' binding groups for potency against DPP IV. In addition, both cyclohexyl glycine (CHG) and octahydroindole carboxylate (OIC) serve as the most potent S2 binding groups within each series. Stereochemistry at the alpha-position of the central ring is relevant to potency within the ketopyrrolidines series, but not in the ketoazetidine series. Finally, the ketoazetidines display enhanced stability over the corresponding ketopyrrolidines, while maintaining their potency. In fact, certain stabilized ketoazetidines can maintain their in vitro potency and inhibit DPP IV in the plasma for up to 6h. 相似文献
92.
Effect of Cecropin B and a Synthetic Analogue on Propagation of Fish Viruses In Vitro 总被引:2,自引:0,他引:2
Abstract Cecropins and other natural antimicrobial peptides are widely distributed in animals from insects to mammals. These
proteins have been shown to be major constituents of the innate immune systems of animals for nonspecific defense of the host
against various bacteria and parasites. Therefore, exploitation of this natural innate defense system may lead to the development
of effective methods for protecting fish from invasion by microbial pathogens. Recently, we have demonstrated that the introduction
of cecropin transgenes into Japanese medaka (Oryzias latipes) conferred resistance to infection by fish bacterial pathogens.
Aside from a few reports documenting the antiviral effect of antimicrobial peptides including cecropins against mammalian
viruses, there is no evidence for the effect of these peptides against fish viruses. In this article we present results of
in vitro characterization of native cecropin B and a synthetic analogue, CF17, against several important fish viral pathogens—namely,
infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia virus (VHSV), snakehead rhabdovirus (SHRV), and
infectious pancreatic necrosis virus (IPNV). Upon coincubation of these peptides and viruses, the viral titers yielded in
fish cells were reduced from several fold to 104-fold. Direct disruption of the viral envelope and disintegration of the viral
capsids may be involved in the inhibition of viral replication by the peptides. Results of our studies demonstrate the potential
of manipulating antimicrobial peptide genes by transgenesis to combat viral infection in fish. 相似文献
93.
94.
The detection of rare mutant DNA from a background of wild-type alleles usually requires laborious manipulations, such as restriction enzyme digestion and gel electrophoresis. Here, we describe a protocol for homogeneous detection of rare mutant DNA in a single tube. The protocol uses a peptide nucleic acid (PNA) as both PCR clamp and sensor probe. The PNA probe binds tightly to perfectly matched wild-type DNA template but not to mismatched mutant DNA sequences, which specifically inhibits the PCR amplification of wild-type alleles without interfering with the amplification of mutant DNA. A fluorescein tag (which undergoes fluorescence resonance energy transfer with the adjacent fluorophore of an anchor probe when both are annealed to the template DNA) also allows the PNA probe to generate unambiguous melting curves to detect mutant DNA during real-time fluorescent monitoring. The whole assay takes about only 1 h. This protocol has been used for detecting mutant K-ras DNA and could be applied to the detection of other rare mutant DNAs. 相似文献
95.
• Background and Aims The genetic variation and divergence estimated by allozyme analysis were used to reveal the evolutionary history of Castanopsis carlesii in Taiwan. Two major questions were discussed concerning evolutionary issues: where are the diversity centres, and where are the most genetically divergent sites in Taiwan?• Methods Twenty-two populations of C. carlesii were sampled throughout Taiwan. Starch gel electrophoresis was used to assay allozyme variation. Genetic parameters and mean FST values of each population were analysed using the BIOSYS-2 program. Mean FST values of each population against the remaining populations, considered as genetic divergence, were estimated using the FSTAT program.• Key Results Average values of genetic parameters describing the within-population variation, the average number of alleles per locus (A = 2·5), the effective number of alleles per locus (Ae = 1·38), the allelic richness (Ar = 2·38), the percentage of polymorphic loci (P = 69 %), and the expected heterozygosity (He = 0·270) were estimated. High levels of genetic diversity were found for C. carlesii compared with other local plant species. Genetic differentiation between populations was generally low.• Conclusions From the data of expected heterozygosity, one major diversity centre was situated in central Taiwan corroborating previous reports for other plant species. According to the mean FST value of each population, the most divergent populations were situated in two places. One includes populations located in north central Taiwan between 24·80°N and 24·20°N. The other is located in south-eastern Taiwan between 22·40°N and 23·10°N. These two regions are approximately convergent with the most divergent locations determined for several other plant species using chloroplast DNA markers published previously. An important finding obtained from this study is that unordered markers like allozymes can be used to infer past population histories as well as chloroplast DNA markers do. 相似文献
96.
97.
Tsai KL Huang YH Kao CL Yang DM Lee HC Chou HY Chen YC Chiou GY Chen LH Yang YP Chiu TH Tsai CS Ou HC Chiou SH 《The Journal of nutritional biochemistry》2012,23(5):458-468
BackgroundAtherosclerosis is a chronic inflammatory disease of the vessel wall associated with oxidized low-density lipoprotein (oxLDL)-induced apoptosis of endothelial cells. Coenzyme Q10 (CoQ10), a potent antioxidant and a critical intermediate of the electron transport chain, has been reported to inhibit LDL oxidation and thus the progression of atherosclerosis. However, its molecular mechanisms on endothelial cells remain still unclarified.MethodsIn this study, primary human umbilical vein endothelial cell cultures treated with oxLDL were used to explore the protective effects of CoQ10.ResultsOur results showed that CoQ10 attenuated the oxLDL-induced generation of reactive oxygen species and improved the antioxidant capacity. CoQ10 also attenuated the oxLDL-mediated down-regulation of endothelial nitric oxide synthase (eNOS) and up-regulation of inducible nitric oxide synthase (iNOS). In addition, CoQ10 suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, release of proinflammatory cytokines and the adherence of monocytic THP-1 cells. Moreover, CoQ10 attenuated oxLDL-altered proapoptotic responses. The inhibitor of eNOS (l-NIO 10 μM) and iNOS (1400W 10 μM) as well as NO enhancer (SNP 10 μM) were used to clean up the mechanism.ConclusionThese results provide new insight into the possible molecular mechanisms by which CoQ10 protects against atherogenesis by NO-related pathways. 相似文献
98.
99.
Yin‐Quan Chen Pei‐lun Chou Chen‐Yu Cheng Chia‐Chun Chiang Ming‐Tzo Wei Chin‐Ting Chuang Yi‐Lin Sophia Chen Arthur Chiou 《Journal of biophotonics》2012,5(10):777-784
The viscoelastic properties of synovial fluid (SF) are critical to its functions of lubrication and shock‐absorption of joints in human body; a change in the viscoelastic properties, even of only a few percents, is often concomitant with arthritis. In this work, the elastic modulus G ′(f) and the viscous modulus G ′′(f) of SF from patients suffering from three kinds of joint diseases, namely, osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), were determined as a function of frequency “f ” (in the low frequency range from f ~ 0.1 to 10 Hz) by Diffusing Wave Spectroscopy (DWS) and correlated with the white blood cell (WBC) count. A strong correlation was observed, showing a higher WBC count corresponding to lower elastic and viscous moduli, G ′ and G ′′; further details depend on inflammatory vs. non‐inflammatory, and on the severity of inflammation. Different types of arthritis lead to different degrees of decreasing viscoelasticity. Identical measurements were carried out with a commercial visco‐supplementation (or artificial SF) to serve as reference. In general, the reduction in both G ′ and G ′′ was most severe in the case of GA and least severe in the case of OA. Besides, in all cases, the reduction in G ′ was more prominent than the reduction in G ′′, indicating that in general, the deterioration in the elasticity of SF by inflammation is more severe than that in the viscosity. This simple method for quantitative physical characterization of synovial fluid may serve as a useful complementary metric to the conventional biochemical analysis in clinical diagnosis of arthritis. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
100.
Che-Chang Chan Ling-Yi Cheng Jean Lu Yi-Hsiang Huang Shih-Hwa Chiou Ping-Hsing Tsai Teh-Ia Huo Han-Chieh Lin Fa-Yauh Lee 《PloS one》2012,7(12)