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941.
942.
Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis. 相似文献
943.
He YQ Zhang L Jiang BL Zhang ZC Xu RQ Tang DJ Qin J Jiang W Zhang X Liao J Cao JR Zhang SS Wei ML Liang XX Lu GT Feng JX Chen B Cheng J Tang JL 《Genome biology》2007,8(10):R218-26
Background
Xanthomonas campestris pathovar campestris (Xcc) is the causal agent of black rot disease of crucifers worldwide. The molecular genetic diversity and host specificity of Xcc are poorly understood.Results
We constructed a microarray based on the complete genome sequence of Xcc strain 8004 and investigated the genetic diversity and host specificity of Xcc by array-based comparative genome hybridization analyses of 18 virulent strains. The results demonstrate that a genetic core comprising 3,405 of the 4,186 coding sequences (CDSs) spotted on the array are conserved and a flexible gene pool with 730 CDSs is absent/highly divergent (AHD). The results also revealed that 258 of the 304 proved/presumed pathogenicity genes are conserved and 46 are AHD. The conserved pathogenicity genes include mainly the genes involved in type I, II and III secretion systems, the quorum sensing system, extracellular enzymes and polysaccharide production, as well as many other proved pathogenicity genes, while the AHD CDSs contain the genes encoding type IV secretion system (T4SS) and type III-effectors. A Xcc T4SS-deletion mutant displayed the same virulence as wild type. Furthermore, three avirulence genes (avrXccC, avrXccE1 and avrBs1) were identified. avrXccC and avrXccE1 conferred avirulence on the hosts mustard cultivar Guangtou and Chinese cabbage cultivar Zhongbai-83, respectively, and avrBs1 conferred hypersensitive response on the nonhost pepper ECW10R.Conclusion
About 80% of the Xcc CDSs, including 258 proved/presumed pathogenicity genes, is conserved in different strains. Xcc T4SS is not involved in pathogenicity. An efficient strategy to identify avr genes determining host specificity from the AHD genes was developed. 相似文献944.
945.
Lim BO Lee JH Ko NY Mun SH Kim JW Kim do K Kim JD Kim BK Kim HS Her E Lee HY Choi WS 《Experimental biology and medicine (Maywood, N.J.)》2007,232(11):1425-1431
The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/- 2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow-derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells. 相似文献
946.
947.
Duan Xiaojing Zhu Zhonglong Yang Yang Duan Jie Jia Zhongkui Chen Faju Sang Ziyang Ma Luyi 《Journal of Plant Growth Regulation》2022,41(1):227-235
Journal of Plant Growth Regulation - To improving the understand of the accumulation pattern of soluble sugars in Magnolia wufengensis during natural cold acclimation, the dynamics of freezing... 相似文献
948.
Deng Kun Li Li Li Linling Xu Feng Yuan Honghui Zha Sanxing Xiao Xian Yu Jie Cheng Shuiyuan Cheng Hua 《Plant Molecular Biology Reporter》2022,40(2):232-246
Plant Molecular Biology Reporter - Flavonoids from Ginkgo biloba have antioxidant and free radical scavenging activity. In the present study, we used different concentrations of OS (organic... 相似文献
949.
Molecular and Cellular Biochemistry - Pyrin and hematopoietic expression, interferon-inducible nature, and nuclear localization (HIN) domain family member 1 (PYHIN1), also known as IFIX, belongs to... 相似文献
950.
Wang Ning Gao Qing Shi Jie Yulan Chen Ji Weimeng Sheng Xiumei Zhang Rui 《Molecular biology reports》2022,49(9):8727-8740
Molecular Biology Reports - During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic β-cells. To battle against the... 相似文献