全文获取类型
收费全文 | 19400篇 |
免费 | 1434篇 |
国内免费 | 1534篇 |
出版年
2024年 | 34篇 |
2023年 | 290篇 |
2022年 | 656篇 |
2021年 | 1105篇 |
2020年 | 680篇 |
2019年 | 920篇 |
2018年 | 815篇 |
2017年 | 569篇 |
2016年 | 891篇 |
2015年 | 1173篇 |
2014年 | 1475篇 |
2013年 | 1540篇 |
2012年 | 1845篇 |
2011年 | 1590篇 |
2010年 | 1005篇 |
2009年 | 865篇 |
2008年 | 962篇 |
2007年 | 826篇 |
2006年 | 670篇 |
2005年 | 591篇 |
2004年 | 491篇 |
2003年 | 446篇 |
2002年 | 392篇 |
2001年 | 288篇 |
2000年 | 292篇 |
1999年 | 308篇 |
1998年 | 201篇 |
1997年 | 201篇 |
1996年 | 191篇 |
1995年 | 155篇 |
1994年 | 137篇 |
1993年 | 96篇 |
1992年 | 141篇 |
1991年 | 116篇 |
1990年 | 101篇 |
1989年 | 78篇 |
1988年 | 56篇 |
1987年 | 31篇 |
1986年 | 31篇 |
1985年 | 41篇 |
1984年 | 18篇 |
1983年 | 23篇 |
1982年 | 12篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1965年 | 1篇 |
1963年 | 1篇 |
1962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
991.
Xiaoxiao Zhang Wenjuan Dong Xun Wang Zhenbang Zhu Sheng He Hui Zhang Yaosheng Chen Xiaohong Liu Chunhe Guo 《The Journal of biological chemistry》2022,298(2)
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a serious threat to the swine industry worldwide. Exostosin glycosyltransferase 1 (EXT1), an enzyme involved in the biosynthesis of heparin sulfate, has also been reported to be a host factor essential for a wide variety of pathogens. However, the role of EXT1 in PRRSV infection remains uncharted. Here, we identified that PRRSV infection caused an increase of EXT1 expression. EXT1 knockdown promoted virus infection, whereas its overexpression inhibited virus infection, suggesting an inhibitory function of EXT1 to PRRSV infection. We found that EXT1 had no effects on the attachment, internalization, or release of PRRSV but did restrict viral RNA replication. EXT1 was determined to interact with viral nonstructural protein 3 (nsp3) and nsp5 via its N-terminal cytoplasmic tail and to enhance K48-linked polyubiquitination of these two nsps to promote their degradation. Furthermore, the C-terminal glycosyltransferase activity domain of EXT1 was necessary for nsp3 and nsp5 degradation. We also found that EXT2, a EXT1 homolog, interacted with EXT1 and inhibited PRRSV infection. Similarly, EXT1 effectively restricted porcine epidemic diarrhea virus and porcine enteric alphacoronavirus infection in Vero cells. Taken together, this study reveals that EXT1 may serve as a broad-spectrum host restriction factor and suggests a molecular basis for the potential development of therapeutics against PRRSV infection. 相似文献
992.
993.
Chong Zhou Xi He Chang Tong Honghui Li Caifeng Xie Yudong Wu Lieliang Wang Xiaohua Yan Daya Luo Yunpeng Tang Zhongman Cheng Xiangyang Xiong 《International journal of biological sciences》2022,18(4):1363
Cancer-associated adipocytes (CAAs), which are adipocytes transformed by cancer cells, are of great importance in promoting the progression of breast cancer. However, the underlying mechanisms involved in the crosstalk between cancer cells and adipocytes are still unknown. Here we report that CAAs and breast cancer cells communicate with each other by secreting the cytokines leukemia inhibitory factor (LIF) and C-X-C subfamily chemokines (CXCLs), respectively. LIF is a pro-inflammatory cytokine secreted by CAAs, which promotes migration and invasion of breast cancer cells via the Stat3 signaling pathway. The activation of Stat3 induced the secretion of glutamic acid-leucine-arginine (ELR) motif CXCLs (CXCL1, CXCL2, CXCL3 and CXCL8) in tumor cells. Interestingly, CXCLs in turn activated the ERK1/2/NF-κB/Stat3 signaling cascade to promote the expression of LIF in CAAs. In clinical breast cancer pathology samples, the up-regulation of LIF in paracancerous adipose tissue was positively correlated with the activation of Stat3 in breast cancer. Furthermore, we verified that adipocytes enhanced lung metastasis of breast cancer cells, and the combination of EC330 (targeting LIF) and SB225002 (targeting C-X-C motility chemokine receptor 2 (CXCR2)) significantly reduced lung metastasis of breast cancer cells in vivo. Our findings reveal that the interaction of adipocytes with breast cancer cells depends on a positive feedback loop between the cytokines LIF and CXCLs, which promotes breast cancer invasion and metastasis. 相似文献
994.
Xiaoyan Hao Yuan Guo Rui Wang Xueyuan Yu Lin He Maoguo Shu 《Acta biochimica et biophysica Sinica》2021,(4):501-510
The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years.Owing to their anti-inflammatory ef... 相似文献
995.
Huimin Wang Feng Jiang Xiang Liu Qing Liu Yunyun Fu Ran Li Li Hou Jie Zhang Jing He Le Kang 《EMBO reports》2022,23(3)
Animal feeding, which directly affects growth and metabolism, is an important physiological process. However, the contribution of PIWI proteins and PIWI‐interacting RNAs (piRNAs) to the regulatory mechanism of animal feeding is unknown. Here, we report a novel function of Piwi and piRNAs in regulating food intake in locusts. Our study shows that the locust can serve as a representative species for determining PIWI function in insects. Knockdown of Piwi1 expression suppresses anabolic processes and reduces food consumption and body weight. The reduction in food intake by knockdown of Piwi1 expression results from decreased expression of neuropeptide NPF1 in a piRNA‐dependent manner. Mechanistically, intronic piRNAs might enhance RNA splicing of NPF1 by preventing hairpin formation at the branch point sites. These results suggest a novel nuclear PIWI/piRNA‐mediated mechanism that controls food intake in the locust nervous system. 相似文献
996.
997.
998.
Animal studies indicated that P1 promoter–driven hepatocyte nuclear factor 4 alpha (HFN4A) prevents carcinogenesis in colitis. But the function of total HNF4A protein has not been fully investigated, and it was assumed to be involved in the colitis-neoplastic sequence. The aim of this study was to determine the clinical value of total P1-/P2-driven HNF4A combined with β-catenin in the colitis-neoplastic sequence. A total of 69 samples, including 4 normal colon tissues, 16 sporadic colorectal cancer (CRC) tissues, 35 inflammatory bowel disease (IBD) tissues, and 14 IBD-associated low-grade dysplasia tissues, were collected to assess P1-/P2-driven HNF4A and β-catenin expressions by immunohistochemical assay. In addition, a colonic epithelial cell line Caco2 with stable P1-/P2-driven HNF4A knockdown was constructed. β-Catenin expression and skeleton structure were determined in the transfected cells by western blot analysis and immunofluorescence assay respectively. Increased expression of nuclear P1-/P2-driven HNF4A was observed in the colitis-associated colorectal neoplasm and sporadic CRC samples, compared with that in colitis samples. The parallel alterations between cytoplasmic β-catenin and nuclear P1-/P2-driven HNF4A were also verified. Silencing of P1-/P2-driven HNF4A expression in Caco2 cells decreased β-catenin expression and F-actin formation. Our results confirmed the elevated expressions of nuclear P1-/P2-driven HNF4A and cytoplasmic β-catenin in the colitis-neoplastic sequence, and both of them may be used as potential biomarkers to predict low-grade dysplasia. 相似文献
999.
绿原酸是灰毡毛忍冬生长发育过程中产生的重要的次级代谢产物,而CCoA OMT是绿原酸合成过程中的关键基因.为进一步揭示灰毡毛忍冬LmCCoA OMT基因的功能,本研究利用RACE技术克隆LmC-CoA OMT全长基因,通过生物信息学进行分析,并在大肠杆菌中表达该蛋白.此外,通过RT-qPCR和HPLC的方法研究CCoA... 相似文献
1000.
Yuting Zhang Hongxia Gao Xiaohui Hu Qisheng Wang Fanglin Zhong Xuelan Zhou Cheng Lin Yang Yang Junkang Wei Weian Du Huaiqiu Huang Huan Zhou Wei He Hua Zhang Yuting Zhang Peter J. McCormick Jinheng Fu Dan Wang Yang Fu Xiaolu Lu Tengfei Zhang Jingjing Duan Bingjie Qin Haihai Jiang Jun Luo Yan Zhang Qi Chen Qunfeng Luo Lin Cheng Zheng Zhang Jin Zhang Jian Li 《Journal of virology》2022,96(1)