全文获取类型
收费全文 | 22236篇 |
免费 | 1983篇 |
国内免费 | 2295篇 |
出版年
2024年 | 30篇 |
2023年 | 187篇 |
2022年 | 399篇 |
2021年 | 705篇 |
2020年 | 595篇 |
2019年 | 688篇 |
2018年 | 687篇 |
2017年 | 581篇 |
2016年 | 782篇 |
2015年 | 1260篇 |
2014年 | 1459篇 |
2013年 | 1610篇 |
2012年 | 2042篇 |
2011年 | 1764篇 |
2010年 | 1256篇 |
2009年 | 1156篇 |
2008年 | 1435篇 |
2007年 | 1304篇 |
2006年 | 1229篇 |
2005年 | 1131篇 |
2004年 | 1042篇 |
2003年 | 950篇 |
2002年 | 796篇 |
2001年 | 555篇 |
2000年 | 463篇 |
1999年 | 428篇 |
1998年 | 278篇 |
1997年 | 212篇 |
1996年 | 194篇 |
1995年 | 171篇 |
1994年 | 149篇 |
1993年 | 110篇 |
1992年 | 138篇 |
1991年 | 109篇 |
1990年 | 91篇 |
1989年 | 89篇 |
1988年 | 59篇 |
1987年 | 70篇 |
1986年 | 53篇 |
1985年 | 28篇 |
1984年 | 18篇 |
1983年 | 35篇 |
1982年 | 16篇 |
1981年 | 17篇 |
1979年 | 17篇 |
1978年 | 14篇 |
1977年 | 13篇 |
1975年 | 10篇 |
1972年 | 12篇 |
1970年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
921.
Truong Xuan Dai Hoang Nghia Son Ho Nguyen Quynh Chi Hoang Nghia Quang Huy Nguyen Thai Minh Nguyen Thi Thuy Tram Nguyen Thi Thuong Huyen To Minh Quan Doan Chinh Chung Truong Hai Nhung Tran Thi Minh Tran Hong Diem Nguyen Thi Phuong Mai Le Thanh Long 《Current issues in molecular biology》2021,43(3):2210
Astronauts are always faced with serious health problems during prolonged spaceflights. Previous studies have shown that weightlessness significantly affects the physiological function of female astronauts, including a change in reproductive hormones and ovarian cells, such as granulosa and theca cells. However, the effects of microgravity on these cells have not been well characterized, especially in granulosa cells. This study aimed to investigate the effects of simulated microgravity (SMG) on the proliferation and morphology of porcine granulosa cells (pGCs). pGC proliferation from the SMG group was inhibited, demonstrated by the reduced O.D. value and cell density in the WST-1 assay and cell number counting. SMG-induced pGCs exhibited an increased ratio of cells in the G0/G1 phase and a decreased ratio of cells in the S and G2/M phase. Western blot analysis indicated a down-regulation of cyclin D1, cyclin-dependent kinase 4 (cdk4), and cyclin-dependent kinase 6 (cdk6), leading to the prevention of the G1-S transition and inducing the arrest phase. pGCs under the SMG condition showed an increase in nuclear area. This caused a reduction in nuclear shape value in pGCs under the SMG condition. SMG-induced pGCs exhibited different morphologies, including fibroblast-like shape, rhomboid shape, and pebble-like shape. These results revealed that SMG inhibited proliferation and induced morphological changes in pGCs. 相似文献
922.
Shigang Qiao Lei Hong Yongming Zhu Jun Zha An Wang Jia Qiu Wei Li Chen Wang Jianzhong An Huiling Zhang 《Cell death & disease》2022,13(2)
Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are critical regulators of programmed necrosis or necroptosis. However, the role of the RIPK1/RIPK3 signaling pathway in myocardial fibrosis and related diabetic cardiomyopathy is still unclear. We hypothesized that RIPK1/RIPK3 activation mediated myocardial fibrosis by impairing the autophagic flux. To this end, we established in vitro and in vivo models of type 2 diabetes mellitus with high glucose fat (HGF) medium and diet respectively. HGF induced myocardial fibrosis, and impaired cardiac diastolic and systolic function by activating the RIPK1/RIPK3 pathway, which increased the expression of autophagic related proteins such as LC3-II, P62 and active-cathepsin D. Inhibition of RIPK1 or RIPK3 alleviated HGF-induced death and fibrosis of cardiac fibroblasts by restoring the impaired autophagic flux. The autophagy blocker neutralized the effects of the RIPK1 inhibitor necrostatin-1 (Nec-1) and RIPK3 inhibitor GSK872 (GSK). RIPK1/RIPK3 inhibition respectively decreased the levels of RIPK3/p-RIPK3 and RIPK1/p-RIPK1. P62 forms a complex with RIPK1-RIPK3 and promotes the binding of RIPK1 and RIPK3, silencing of RIPK1 decreased the association of RIPK1 with P62 and the binding of P62 to LC3. Furthermore, inhibition of both kinases in combination with a low dose of Nec-1 and GSK in the HGF-treated fibroblasts significantly decreased cell death and fibrosis, and restored the autophagic flux. In the diabetic rat model, Nec-1 (1.65 mg/kg) treatment for 4 months markedly alleviated myocardial fibrosis, downregulated autophagic related proteins, and improved cardiac systolic and diastolic function. In conclusion, HGF induces myocardial fibrosis and cardiac dysfunction by activating the RIPK1-RIPK3 pathway and by impairing the autophagic flux, which is obviated by the pharmacological and genetic inhibition of RIPK1/RIPK3.Subject terms: Necroptosis, Diabetes complications 相似文献
923.
924.
Andrew E Rosselot Miri Park Mari Kim Toru MatsuUra Gang Wu Danilo E Flores Krithika R Subramanian Suengwon Lee Nambirajan Sundaram Taylor R Broda Heather A McCauley Jennifer A Hawkins Kashish Chetal Nathan Salomonis Noah F Shroyer Michael A Helmrath James M Wells John B Hogenesch Sean R Moore Christian I Hong 《The EMBO journal》2022,41(2)
925.
926.
927.
928.
929.
Lin Peng Min Zhao Tianqi Liu Jiangbo Chen Pin Gao Lei Chen Pu Xing Zaozao Wang Jiabo Di Qiang Xu Hong Qu Beihai Jiang Xiangqian Su 《Cell death & disease》2022,13(4)
Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.Subject terms: Cancer genomics, Colorectal cancer, Metastasis, Oncogenes, Cell signalling 相似文献
930.