全文获取类型
收费全文 | 8924篇 |
免费 | 695篇 |
国内免费 | 854篇 |
专业分类
10473篇 |
出版年
2024年 | 41篇 |
2023年 | 169篇 |
2022年 | 370篇 |
2021年 | 606篇 |
2020年 | 388篇 |
2019年 | 441篇 |
2018年 | 445篇 |
2017年 | 330篇 |
2016年 | 415篇 |
2015年 | 585篇 |
2014年 | 662篇 |
2013年 | 693篇 |
2012年 | 846篇 |
2011年 | 738篇 |
2010年 | 462篇 |
2009年 | 391篇 |
2008年 | 427篇 |
2007年 | 377篇 |
2006年 | 323篇 |
2005年 | 271篇 |
2004年 | 217篇 |
2003年 | 183篇 |
2002年 | 151篇 |
2001年 | 106篇 |
2000年 | 114篇 |
1999年 | 107篇 |
1998年 | 84篇 |
1997年 | 86篇 |
1996年 | 56篇 |
1995年 | 56篇 |
1994年 | 71篇 |
1993年 | 36篇 |
1992年 | 38篇 |
1991年 | 33篇 |
1990年 | 25篇 |
1989年 | 32篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 12篇 |
1985年 | 20篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
931.
Dong Xiao Anandan Palani Xianhai Huang Michael Sofolarides Wei Zhou Xiao Chen Robert Aslanian Zhuyan Guo James Fossetta Fang Tian Prashant Trivedi Peter Spacciapoli Charles E. Whitehurst Daniel Lundell 《Bioorganic & medicinal chemistry letters》2013,23(11):3262-3266
Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay. 相似文献
932.
Qingqing Cai Huiqiang Huang Dong Qian Kailin Chen Junhua Luo Ying Tian Tianxin Lin Tongyu Lin 《PloS one》2013,8(6)
13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin’s lymphoma (T-NHL) cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8) assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells). Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product) were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB) phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas. 相似文献
933.
对从小麦-黑麦代换系5R/5A与1R/1D杂交后代中选育的大穗型品系1-5、1-6、1-7、1-8、1-9、1-10、1-11进行形态学与SSR分析。结果表明,7个品系田间表现遗传性稳定,且具有黑麦大穗、抗病等优良性状;利用黑麦特异引物PSC119.1确定7个品系均导入了黑麦染色体片段,引物SCM138扩增结果表明,在1-6、1-7、1-8、1-9、1-10中导入了黑麦染色体5RS片段,引物SCM120、TSM604可以在7个品系中稳定扩增出黑麦5R长臂和1R短臂特异片段。以上结果可为小麦遗传育种与品质改良提供基础材料。 相似文献
934.
RIP3 deficiency exacerbates inflammation in dextran sodium sulfate‐induced ulcerative colitis mice model 下载免费PDF全文
Yu‐Lin Xu Hai‐Lin Tang Shi‐Ying Zhu Hao‐Ran Peng Zhong‐Tian Qi Wen Wang 《Cell biochemistry and function》2017,35(3):156-163
Ulcerative colitis (UC) is a chronic intestinal inflammatory disease. The receptor‐interacting protein kinase 3 (RIP3) was reported to be involved in many inflammatory disease. However, the mechanism of RIP3 in the pathogenesis of UC is still unclear. To investigate the effects and possible mechanism of RIP3 in UC pathogenesis, RIP3‐/‐ mice was used in dextran sulfate sodium (DSS)‐induced colitis model. It was found that by DSS‐induced colitis, RIP3‐/‐ mice showed significantly enhanced colitis symptoms, including increased weight loss, colon shortening, and colonic mucosa damage and severity, but decreased production of interleukin 6 and interleukin 1β. The results showed that RIP3 deficiency could not ameliorate but exacerbate the severity of colitis. On the mechanism, it was found that messenger RNA expressions of several repair‐associated cytokines including interleukin 6, interleukin 22, cyclooxygenase 2, epithelial growth factor receptor ligand Epiregulin and matrix metalloproteinase 10 were siginificant decreased in RIP3‐/‐ mice. Thus, RIP3‐/‐ mice exhibited an impaired tissue repair in response to DSS. In a conclusion, RIP3 deficiency exerted detrimental effects in DSS induced colitis partially because of the impaired repair‐associated cytokines expression. 相似文献
935.
936.
Rongjun Shi Honghui Huang Zhanhui Qi Weian Hu Ziyang Tian Ming Dai 《World journal of microbiology & biotechnology》2013,29(1):153-162
Four marine bacterial strains P1, P5, N5 and N21 were isolated from the surface water and sediment of Mirs Bay in southern Chinese coast using the liquid infection method with 48-well plates. These bacteria were all shown to have algicidal activities against Skeletonema costatum. Based on morphological observations, biochemical tests and homology comparisons by 16S rDNA sequences, the isolated strains P1, P5, N5 and N21 were identified as Halobacillus sp., Muricauda sp., Kangiella sp. and Roseivirga sp., respectively. Our results showed that bacterial strain P1 killed S. costatum by release of heat labile algicide, while strains P5, N5 and N21 killed them directly. The algicidal processes of four bacterial strains were different. Strains P1, N5 and N21 disrupted the chain structure and S. costatum appeared as single cells, in which the cellular components were aggregated and the individual cells were inflated and finally lysed, while strain P5 decomposed the algal chains directly. We also showed that the algicidal activities of the bacterial strains were concentration-dependent. More specifically, 10?% (v/v) of bacteria in algae showed the strongest algicidal activities, as all S. costatum cells were killed by strains N5 and N21 within 72?h and by strains P1 and P5 within 96?h. 5?% of bacteria in algae also showed significant algicidal activities, as all S. costatum were killed by strains N5, P5 and N21 within 72, 96 and 120?h, respectively, whereas at this concentration, only 73.4?% of S. costatum cells exposed to strain P1 were killed within 120?h. At the concentration of 1?% bacteria in algae, the number of S. costatum cells continued to increase and the growth rate of algae upon exposure to strain N5 was significantly inhibited. 相似文献
937.
Jason Hilton Shi-Jun Wang Wei-Qing Zhu Baolin Tian Jean Galtier An-Hua Wei 《Review of Palaeobotany and Palynology》2002,120(3-4):301-314
A distinctive kind of anatomically preserved cardiocarpalean ovule is described from the Early Permian Taiyuan Formation of northern China. Ovules are small, have 180° rotational symmetry, and possess variably thick integuments with prominent secretory cavities that may be empty, filled with resinous materials and in several instances appear to contain animal coprolites. Comparisons show that (where known) these features conform to those of Callospermarion undulatum (Neely) Rothwell, to which they are assigned, previously only known from the Pennsylvanian of Euramerica. These fossils represent the first indisputable occurrence of the genus Callospermarion in the Early Permian Cathaysian floras, and show the presence of callistophytalean seed-ferns in this palaeofloristic realm for the first time. These data combined with results from previous investigations now support the Early Permian northern Cathaysian flora including the Taiyuan Formation having evolved from the Late Carboniferous and earliest Permian Euramerican flora, with which it shares far too many generic level similarities for these co-occurrences to be coincidental. Our hypothesis is therefore that the Early Permian flora of the northern Cathaysian realm represents the continued evolution of wetland Euramerican-type coal-swamp floras, and as such is likely to present a model for evolutionarily driven floral change as opposed to the climatically driven floral changes observed in the Euramerican flora after the demise of coal-swamp environments. The distribution of coprolites in and immediately around glandular cavities in this species suggests specialised syndromes of herbivory existed in Early Permian Cathaysian ecosystems, with herbivores preferentially selecting these areas of the ovule integument. 相似文献
938.
Yanxin Li Xiaoying Chen Yingying Nie Yuhua Tian Xian Xiao Fan Yang 《The Journal of biological chemistry》2021,297(3)
Transient receptor potential vanilloid 1 (TRPV1) ion channel serves as the detector for noxious temperature above 42 °C, pungent chemicals like capsaicin, and acidic extracellular pH. This channel has also been shown to function as an ionotropic cannabinoid receptor. Despite the solving of high-resolution three-dimensional structures of TRPV1, how endocannabinoids such as anandamide and N-arachidonoyl dopamine bind to and activate this channel remains largely unknown. Here we employed a combination of patch-clamp recording, site-directed mutagenesis, and molecular docking techniques to investigate how the endocannabinoids structurally bind to and open the TRPV1 ion channel. We found that these endocannabinoid ligands bind to the vanilloid-binding pocket of TRPV1 in the “tail-up, head-down” configuration, similar to capsaicin; however, there is a unique interaction with TRPV1 Y512 residue critical for endocannabinoid activation of TRPV1 channels. These data suggest that a differential structural mechanism is involved in TRPV1 activation by endocannabinoids compared with the classic agonist capsaicin. 相似文献
939.
Debipreeta Bhowmik Mingjian Du Yuan Tian Siming Ma Jianjun Wu Zhijian Chen Qian Yin Fanxiu Zhu 《Nucleic acids research》2021,49(16):9389
Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that detects aberrant cytosolic DNA arising from pathogen invasions or genotoxic stresses. Upon binding to DNA, cGAS is activated and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which induces potent antimicrobial and antitumor responses. Kaposi sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that causes Kaposi sarcoma and several other malignancies. We previously reported that KSHV inhibitor of cGAS (KicGAS) encoded by ORF52, inhibits cGAS enzymatic activity, but the underlying mechanisms remained unclear. To define the inhibitory mechanisms, here we performed in-depth biochemical and functional characterizations of KicGAS, and mapped its functional domains. We found KicGAS self-oligomerizes and binds to double stranded DNA cooperatively. This self-oligomerization is essential for its DNA binding and cGAS inhibition. Interestingly, KicGAS forms liquid droplets upon binding to DNA, which requires collective multivalent interactions with DNA mediated by both structured and disordered domains coordinated through the self-oligomerization of KicGAS. We also observed that KicGAS inhibits the DNA-induced phase separation and activation of cGAS. Our findings reveal a novel mechanism by which DNA viruses target the host protein phase separation for suppression of the host sensing of viral nucleic acids. 相似文献
940.
Supplementary choline attenuates olive oil lipid emulsion‐induced enterocyte apoptosis through suppression of CELF1/AIF pathway 下载免费PDF全文
Jun‐Kai Yan Jie Zhu Zi‐Zhen Gong Jie Wen Yong‐Tao Xiao Tian Zhang Wei Cai 《Journal of cellular and molecular medicine》2018,22(3):1562-1573
Enterocyte apoptosis induced by lipid emulsions is a key cause of intestinal atrophy under total parenteral nutrition (TPN) support, and our previous work demonstrated that olive oil lipid emulsion (OOLE) could induce enterocyte apoptosis via CUGBP, Elav‐like family member 1 (CELF1)/ apoptosis‐inducing factor (AIF) pathway. As TPN‐associated complications are partially related to choline deficiency, we aimed to address whether choline supplementation could attenuate OOLE‐induced enterocyte apoptosis. Herein we present evidence that supplementary choline exhibits protective effect against OOLE‐induced enterocyte apoptosis both in vivo and in vitro. In a rat model of TPN, substantial reduction in apoptotic rate along with decreased expression of CELF1 was observed when supplementary choline was added to OOLE. In cultured Caco‐2 cells, supplementary choline attenuated OOLE‐induced apoptosis and mitochondria dysfunction by suppressing CELF1/AIF pathway. Compared to OOLE alone, the expression of CELF1 and AIF was significantly decreased by supplementary choline, whereas the expression of Bcl‐2 was evidently increased. No obvious alterations were observed in Bax expression and caspase‐3 activation. Mechanistically, supplementary choline repressed the expression of CELF1 by increasing the recruitment of CELF1 mRNA to processing bodies, thus resulting in suppression of its protein translation. Taken together, our data suggest that supplementary choline exhibits effective protection against OOLE‐induced enterocyte apoptosis, and thus, it has the potential to be used for the prevention and treatment of TPN‐induced intestinal atrophy. 相似文献