全文获取类型
收费全文 | 3795篇 |
免费 | 340篇 |
国内免费 | 325篇 |
专业分类
4460篇 |
出版年
2024年 | 7篇 |
2023年 | 45篇 |
2022年 | 111篇 |
2021年 | 201篇 |
2020年 | 131篇 |
2019年 | 165篇 |
2018年 | 155篇 |
2017年 | 123篇 |
2016年 | 184篇 |
2015年 | 224篇 |
2014年 | 248篇 |
2013年 | 280篇 |
2012年 | 320篇 |
2011年 | 289篇 |
2010年 | 185篇 |
2009年 | 165篇 |
2008年 | 205篇 |
2007年 | 154篇 |
2006年 | 167篇 |
2005年 | 145篇 |
2004年 | 136篇 |
2003年 | 107篇 |
2002年 | 115篇 |
2001年 | 97篇 |
2000年 | 85篇 |
1999年 | 79篇 |
1998年 | 46篇 |
1997年 | 44篇 |
1996年 | 38篇 |
1995年 | 34篇 |
1994年 | 28篇 |
1993年 | 21篇 |
1992年 | 19篇 |
1991年 | 23篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有4460条查询结果,搜索用时 15 毫秒
951.
952.
Hongyu Chen Jinjin Zhang Jinwei Ren Wenzhao Wang Weiping Xiong Yaodong Zhang Li Bao Hongwei Liu 《化学与生物多样性》2018,15(5)
Ganoderma leucocontextum is a well‐known medicinal mushroom cultivated in the Tibet Plateau of China. Chemistry investigation on the fruiting bodies of this mushroom resulted in the isolation of sixteen secondary metabolites including three new lanostane triterpenes, ganoleucoins Q – S ( 1 – 3 ), as well as thirteen known compounds ( 4 – 16 ). The structures of compounds 1 – 3 were determined by NMR, MS, CD spectral analysis, and chemical derivation method. The neuroprotective effects of compounds 1 – 16 were tested on PC12 cells. Compounds 1 and 2 showed protective effects against the H2O2 induced damage with the survival rate of 83.19 ± 0.92%, 73.37 ± 1.25% at the concentration of 200 μm , respectively. Meanwhile, compounds 1 and 2 induced neurite outgrowth at 50 – 200 μm . The results from this study suggested that G. leucocontextum and its metabolites may be potential functional food ingredients for the prevention of neurodegenerative diseases. 相似文献
953.
Bao J Miao S Kayser F Kotliar AJ Baker RK Doss GA Felix JP Bugianesi RM Slaughter RS Kaczorowski GJ Garcia ML Ha SN Castonguay L Koo GC Shah K Springer MS Staruch MJ Parsons WH Rupprecht KM 《Bioorganic & medicinal chemistry letters》2005,15(2):447-451
Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure-activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation. 相似文献
954.
Bao J Hunt JA Miao S Rupprecht KM Stelmach JE Liu L Ruzek RD Sinclair PJ Pivnichny JV Hop CE Kumar S Zaller DM Shoop WL O'neill EA O'keefe SJ Thompson CM Cubbon RM Wang R Zhang WX Thompson JE Doherty JB 《Bioorganic & medicinal chemistry letters》2006,16(1):64-68
Quinolinones and naphthyridinones with C7 N-t-butyl piperidine substituents were found to be potent p38 MAP kinase inhibitors. These compounds significantly suppress TNF-alpha release in both cellular and LPS-stimulated whole blood assays. They also displayed excellent PK profiles across three animal species. Quinolinone at 10 mpk showed comparable oral efficacy to that of dexamethasone at 1 mpk in a murine collagen-induced arthritis model. 相似文献
955.
John C. Biwot Hua‐Bao Zhang Chen Liu Jun‐Xue Qiao Xiao‐Qiang Yu Yu‐Feng Wang 《Insect Science》2020,27(5):869-882
Wolbachia are Gram‐negative endosymbionts that are known to cause embryonic lethality when infected male insects mate with uninfected females or with females carrying a different strain of Wolbachia, a situation characterized as cytoplasmic incompatibility (CI). However, the mechanism of CI is not yet fully understood, although recent studies on Drosophila melanogaster have achieved great progress. Here, we found that Wolbachia infection caused changes in the expressions of several immunity‐related genes, including significant upregulation of kenny (key), in the testes of D. melanogaster. Overexpression of key in fly testes led to a significant decrease in egg hatch rates when these flies mate with wild‐type females. Wolbachia‐infected females could rescue this embryonic lethality. Furthermore, in key overexpressing testes terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling signal was significantly stronger than in the control testes, and the level of reactive oxygen species was significantly increased. Overexpression of key also resulted in alterations of some other immunity‐related gene expressions, including the downregulation of Zn72D. Knockdown of Zn72D in fly testes also led to a significant decrease in egg hatch rates. These results suggest that Wolbachia might induce the defect in male host fertility by immunity‐related pathways and thus cause an oxidative damage and cell death in male testes. 相似文献
956.
Saitoh F Tian QB Okano A Sakagami H Kondo H Suzuki T 《The Journal of biological chemistry》2004,279(28):29461-29468
Targeting of neuronal nitric-oxide synthase (nNOS) to appropriate sites in a cell is mediated by interactions with its PDZ domain and plays an important role in specifying the sites of reaction of nitric oxide (NO) in the central nervous system. Here we report the identification and characterization of a novel nNOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) (GenBank accession number AB098078), which increases nNOS enzyme activity by targeting the nNOS to the synaptic plasma membrane in a PDZ domain-dependent manner. The deduced NIDD protein consisted of 392 amino acid residues and possessed five transmembrane segments, a zinc finger DHHC domain, and a PDZ-binding motif (-EDIV) at its C-terminal tail. In vitro pull-down assays suggested that the C-terminal tail region of NIDD specifically interacted with the PDZ domain of nNOS. The PDZ dependence was confirmed by an experiment using a deletion mutant, and the interaction was further confirmed by co-sedimentation assays using COS-7 cells transfected with NIDD and nNOS. Both NIDD and nNOS were enriched in synaptosome and synaptic plasma membrane fractions and were present in the lipid raft and postsynaptic density fractions in the rat brain. Co-localization of these proteins was also observed by double staining of the proteins in cultured cortical neurons. Thus, NIDD and nNOS were co-localized in the brain, although the colocalizing regions were restricted, as indicated by the distribution of their mRNA expression. Most important, co-transfection of NIDD and nNOS increased NO-producing nNOS activity. These results suggested that NIDD plays an important role in the regulation of the NO signaling pathway at postsynaptic sites through targeting of nNOS to the postsynaptic membrane. 相似文献
957.
Downregulation of Homeodomain‐Interacting Protein Kinase‐2 Contributes to Bladder Cancer Metastasis by Regulating Wnt Signaling 下载免费PDF全文
958.
Zhang Fan Deng Cheng-Kun Huang Yong-Jie Miao Yi-He Wang Yao-Yi Zhang Ying Qian Zhong-Yi Zhang Wei-Quan Zhou Rui-Dong Lei Bao Shen Xin Wu Xing-Yan Cui Ge Song Jing-Ling Mu Zhi-Hao Zou Ying-Ying 《Neurochemical research》2020,45(8):1769-1780
Neurochemical Research - The mechanism of cognitive dysfunction in diabetes is still unclear. Recently, studies have shown that the cerebellum is involved in cognition. Furthermore,... 相似文献
959.
Microarrays for the detection of HBV and HDV 总被引:6,自引:0,他引:6
Zhaohui S Wenling Z Bao Z Rong S Wenli M 《Journal of biochemistry and molecular biology》2004,37(5):546-551
The increasing pace of development in molecular biology during the last decade has had a direct effect on mass testing and diagnostic applications, including blood screening. We report the model Microarray that has been developed for Hepatitis B virus (HBV) and Hepatitis D virus (HDV) detection. The specific primer pairs of PCR were designed using the Primer Premier 5.00 program according to the conserved regions of HBV and HDV. PCR fragments were purified and cloned into pMD18-T vectors. The recombinant plasmids were extracted from positive clones and the target gene fragments were sequenced. The DNA microarray was prepared by robotically spotting PCR products onto the surface of glass slides. Sequences were aligned, and the results obtained showed that the products of PCR amplification were the required specific gene fragments of HBV, and HDV. Samples were labeled by Restriction Display PCR (RD-PCR). Gene chip hybridizing signals showed that the specificity and sensitivity required for HBV and HDV detection were satisfied. Using PCR amplified products to construct gene chips for the simultaneous clinical diagnosis of HBV and HDV resulted in a quick, simple, and effective method. We conclude that the DNA microarray assay system might be useful as a diagnostic technique in the clinical laboratory. Further applications of RD-PCR for the sample labeling could speed up microarray multi-virus detection. 相似文献
960.