全文获取类型
收费全文 | 15682篇 |
免费 | 1186篇 |
国内免费 | 1522篇 |
专业分类
18390篇 |
出版年
2024年 | 57篇 |
2023年 | 256篇 |
2022年 | 549篇 |
2021年 | 858篇 |
2020年 | 700篇 |
2019年 | 949篇 |
2018年 | 837篇 |
2017年 | 592篇 |
2016年 | 749篇 |
2015年 | 1050篇 |
2014年 | 1186篇 |
2013年 | 1300篇 |
2012年 | 1462篇 |
2011年 | 1368篇 |
2010年 | 816篇 |
2009年 | 743篇 |
2008年 | 822篇 |
2007年 | 760篇 |
2006年 | 647篇 |
2005年 | 563篇 |
2004年 | 474篇 |
2003年 | 373篇 |
2002年 | 303篇 |
2001年 | 111篇 |
2000年 | 125篇 |
1999年 | 115篇 |
1998年 | 91篇 |
1997年 | 99篇 |
1996年 | 75篇 |
1995年 | 52篇 |
1994年 | 42篇 |
1993年 | 32篇 |
1992年 | 21篇 |
1991年 | 20篇 |
1990年 | 15篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 20篇 |
1986年 | 14篇 |
1985年 | 20篇 |
1984年 | 16篇 |
1983年 | 10篇 |
1982年 | 18篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1976年 | 5篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1950年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
251.
Mehdi Khoshneviszadeh Mohammad H. Ghahremani Alireza Foroumadi Ramin Miri Omidreza Firuzi Armin Madadkar-Sobhani Najmeh Edraki Maliheh Parsa Abbas Shafiee 《Bioorganic & medicinal chemistry》2013,21(21):6708-6717
A series of 16 novel 1,2,4-triazine derivatives bearing hydrazone moiety (7a–7p) have been designed, synthesized and evaluated for their activity to inhibit IL-1β and TNF-α production. All compounds are reported for the first time. The chemical structures of all compounds were confirmed by spectroscopic methods and elemental analyzes. Most of the synthesized compounds were proved to have potent anti-cytokine activity and low toxicity on PBMC and MCF-7 cell lines. Compounds 7f, 7k, 7l and 7j presented simultaneously good levels of inhibition of both cytokines. Moreover, compound 7l exhibited good anti-inflammatory effect in carrageenan-induced rat paw edema. The results of Western blotting demonstrated that the anti-cytokine potential of compound 7l is mainly mediated through the inhibition of p38 MAPK signaling pathway. Molecular docking was performed to position compound 7l into p38α binding site in order to explore the potential target. The information of this work might be helpful for the design and synthesis of novel scaffold toward the development of new therapeutic agent to fight against inflammatory diseases. 相似文献
252.
Activation and Functional Analysis of Janus Kinase 2 in BA/F3 Cells Using the Coumermycin/Gyrase B System 总被引:2,自引:0,他引:2 下载免费PDF全文
Mohammad Golam Mohi Ken-ichi Arai Sumiko Watanabe 《Molecular biology of the cell》1998,9(12):3299-3308
Janus kinase 2 (Jak2) protein tyrosine kinase plays an important role in interleukin-3– or granulocyte–macrophage colony-stimulating factor–mediated signal transduction pathways leading to cell proliferation, activation of early response genes, and inhibition of apoptosis. However, it is unclear whether Jak2 can activate these signaling pathways directly without the involvement of cytokine receptor phosphorylation. To investigate the specific role of Jak2 in the regulation of signal transduction pathways, we generated gyrase B (GyrB)–Jak2 fusion proteins, dimerized through the addition of coumermycin. Coumermycin induced autophosphorylation of GyrB–Jak2 fusion proteins, thus bypassing receptor activation. Using different types of chimeric Jak2 molecules, we observed that although the kinase domain of Jak2 is sufficient for autophosphorylation, the N-terminal regions are essential for the phosphorylation of Stat5 and for the induction of short-term cell proliferation. Moreover, coumermycin-induced activation of Jak2 can also lead to increased levels of c-myc and CIS mRNAs in BA/F3 cells stably expressing the Jak2 fusion protein with the intact N-terminal region. Conversely, activation of the chimeric Jak2 induced neither phosphorylation of Shc or SHP-2 nor activation of the c-fos promoter. Here, we showed that the GyrB–Jak2 system can serve as an excellent model to dissect signals of receptor-dependent and -independent events. We also obtained evidence indicating a role for the N-terminal region of Jak2 in downstream signaling events. 相似文献
253.
254.
Moheb Ali Pourgholam Hossein Khara Reza Safari Mohammad Ali Yazdani Sadati Mohammad Sadegh Aramli 《Probiotics and antimicrobial proteins》2017,9(1):32-40
A feeding trial was conducted to investigate the effects of different levels of dietary Lactobacillus plantarum on hemato-immunological parameters and resistance against Streptococcus iniae infection in juvenile Siberian sturgeon Acipenser baerii. Fish (14.6 ± 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 × 107, 1 × 108 and 1 × 109 colony-forming units (cfu) g?1] and a control (non-supplemented basal) diet for 8 weeks. Innate immune responses (immunoglobulin (Ig), alternative complement activity (ACH50) and lysozyme activity) were significantly higher in fish fed the 1 × 108 and 1 × 109 cfu g?1 L. plantarum diet compared to the other groups (P < 0.05). Furthermore, fish fed on various levels of L. plantarum significantly showed higher red blood cell (RBC), hemoglobin (Hb), white blood cell (WBC) and monocyte compared to those of the control group (P < 0.05). At the end of the feeding experiment, some fish were challenged with S. iniae to quantify the level of disease resistance. The mortality after S. iniae challenge was decreased in fish fed a probiotic. These results indicated that dietary supplementation of L. plantarum improved immune response and disease resistance of Siberian sturgeon juvenile. 相似文献
255.
Bin Liu Xin Zheng Jiajun Li Xiong Li Ruimei Wu Jing Yang Wei Liu Gaoping Zhao 《Bioscience reports》2021,41(1)
Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches.Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets.Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways.Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway. 相似文献
256.
果胶甲酯酶的结构与功能研究进展 总被引:1,自引:0,他引:1
果胶甲酯酶(PME)是一种重要的果胶酶,其水解果胶中的甲酯基从而释放甲醇并降低果胶的甲酯化程度。目前在食品加工、茶饮料、造纸等生产工艺中有着广泛的应用前景。随着对PME的深入研究,已报道了几种不同来源的酶晶体结构,对这些已获得的晶体结构进行分析发现,PME属于右手平行β-螺旋结构,其催化残基为2个保守的天冬氨酸和1个谷氨酰胺残基,并且在催化过程中分别起到了一般酸碱、亲核试剂以及稳定中间体的作用。同时对其底物特异性进行分析,初步了解其底物与活性位点的识别机制。文中针对这几个相关方面进行了系统的综述。 相似文献
257.
258.
Mahboudi Somayeh Moosavi-Nasab Marzieh Kazemi Bahram Rahimpour Azam Eskandari Mohammad Hadi Mohammadian Omid Shams Forough 《Molecular biology reports》2021,48(5):4405-4412
Molecular Biology Reports - Monoclonal antibodies (mAbs) are widely employed as invaluable therapeutics for a vast number of human disorders. Several approaches have been introduced for the... 相似文献
259.
Hameed Gul Mengya Qian Mohammad G. Arabzai Tianhui Huang Qiannan Ma Fangyu Xing Wan Cao Tingting Liu Hong Duan Qianlin Xiao Zhizhai Liu 《Phyton》2022,91(7):1429-1443
Kernel size-related traits, including kernel length, kernel width, and kernel thickness, are critical components in determining yield and kernel quality in maize (Zea mays L.). Dissecting the phenotypic characteristics of these traits, and discovering the candidate chromosomal regions for these traits, are of potential importance for maize yield and quality improvement. In this study, a total of 139 F2:3 family lines derived from EHel and B73, a distinct line with extremely low ear height (EHel), was used for phenotyping and QTL mapping of three kernel size-related traits, including 10-kernel length (KL), 10-kernel width (KWid), and 10-kernel thickness (KT). The results showed that only one QTL for KWid, i.e., qKWid9 on Chr9, with a phenotypic variation explained (PVE) of 13.4% was detected between SNPs of AX-86298371 and AX-86298372, while no QTLs were detected for KL and KT across all 10 chromosomes. Four bulked groups of family lines, i.e., Groups I to IV, were constructed with F2:3 family lines according to the phenotypic comparisons of KWid between EHel and B73. Among these four groups, Group I possessed a significantly lower KWid than EHel (P = 0.0455), Group II was similar to EHel (P = 0.34), while both Group III and Group IV were statistically higher than EHel (P < 0.05). Besides, except Group IV exhibited a similar KWid to B73 (P = 0.11), KWid of Groups I to III were statistically lower than B73 (P < 0.00). By comparing the bulked genotypes of the four groups to EHel and B73, a stable chromosomal region on Chr9 between SNPs of AX-86298372 to AX-86263154, entirely covered by qKWid9, was identified to link KWid with the positive allele of increasing phenotypic effect to KWid from B73, similar to that of qKWid9. A large amount of enzyme activity and macromolecule binding-related genes were annotated within this chromosomal region, suggesting qKWid9 as a potential QTL for KWid in maize. 相似文献
260.