全文获取类型
收费全文 | 2300篇 |
免费 | 196篇 |
国内免费 | 238篇 |
出版年
2024年 | 2篇 |
2023年 | 39篇 |
2022年 | 59篇 |
2021年 | 142篇 |
2020年 | 95篇 |
2019年 | 147篇 |
2018年 | 121篇 |
2017年 | 89篇 |
2016年 | 103篇 |
2015年 | 157篇 |
2014年 | 158篇 |
2013年 | 141篇 |
2012年 | 211篇 |
2011年 | 172篇 |
2010年 | 102篇 |
2009年 | 86篇 |
2008年 | 110篇 |
2007年 | 88篇 |
2006年 | 77篇 |
2005年 | 75篇 |
2004年 | 42篇 |
2003年 | 48篇 |
2002年 | 54篇 |
2001年 | 39篇 |
2000年 | 33篇 |
1999年 | 50篇 |
1998年 | 21篇 |
1997年 | 34篇 |
1996年 | 22篇 |
1995年 | 29篇 |
1994年 | 31篇 |
1993年 | 16篇 |
1992年 | 37篇 |
1991年 | 22篇 |
1990年 | 21篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 11篇 |
1983年 | 6篇 |
1982年 | 1篇 |
1981年 | 2篇 |
排序方式: 共有2734条查询结果,搜索用时 15 毫秒
1.
Xiaolei Zhuang Elena Semenova Dragan Maric Robert Craigie 《The Journal of biological chemistry》2014,289(2):1119-1127
Barrier-to-autointegration factor (BAF or BANF1) is highly conserved in multicellular eukaryotes and was first identified for its role in retroviral DNA integration. Homozygous BAF mutants are lethal and depletion of BAF results in defects in chromatin segregation during mitosis and subsequent nuclear envelope assembly. BAF exists both in phosphorylated and unphosphorylated forms with phosphorylation sites Thr-2, Thr-3, and Ser-4, near the N terminus. Vaccinia-related kinase 1 is the major kinase responsible for phosphorylation of BAF. We have identified the major phosphatase responsible for dephosphorylation of Ser-4 to be protein phosphatase 4 catalytic subunit. By examining the cellular distribution of phosphorylated BAF (pBAF) and total BAF (tBAF) through the cell cycle, we found that pBAF is associated with the core region of telophase chromosomes. Depletion of BAF or perturbing its phosphorylation state results not only in nuclear envelope defects, including mislocalization of LEM domain proteins and extensive invaginations into the nuclear interior, but also impaired cell cycle progression. This phenotype is strikingly similar to that seen in cells from patients with progeroid syndrome resulting from a point mutation in BAF. 相似文献
2.
3.
Fenglei Chen Yujing Wang Qinguang Liu Jiahui Hu Jiaqi Jin Zhiyu Ma Jinlong Zhang 《Journal of cellular physiology》2020,235(7-8):5666-5678
ER oxidoreduclin 1α (ERO1α) is an oxidase, participating in formation of secretory and membrane proteins. However, the other physiological functions ERO1α is not well known. We found that ERO1α is high in the Leydig cells of the testis. Therefore, the purposes of the current study are to explore the role of ERO1α and the possible mechanisms in regulating cell proliferation, apoptosis, and testosterone secretion of Leydig cells. ERO1α was mainly localized in Leydig cells in the adult mice testes by immunofluorescence staining. Western blot analysis showed that ERO1α was higher in Leydig cells than that in the seminiferous tubules. The effect of ERO1α on cell proliferation, apoptosis, and testosterone secretion was detected by transducing ERO1α overexpression and knockdown lentiviruses into cultured primary Leydig cells (PLCs) together with hCG exposure. Flow cytometry analysis showed that ERO1α promoted cell proliferation by increasing cell distribution at the S phase and decreasing that at the G0/G1 phase. Western bolt analysis showed that ERO1α increased CDK2 and CDK6 expression. Cell apoptosis determination found that ERO1α inhibited PLC apoptosis. Western bolt analysis showed that ERO1α increased the ratio of BCL-2/BAX, and decreased BAD and Caspase-3 expression. Enzyme-linked immunosorbent assay analysis demonstrated that ERO1α enhanced testosterone secretion. Western bolt analysis found that ERO1α increased StAR, 3β-HSD, and CYP17A1 expression. Furthermore, ERO1α could activate the PI3K/AKT/mTOR signaling pathway. In summary, these results suggest that ERO1α might play proliferation promotion and antiapoptotic roles and enhance testosterone secretion in PLC, at least partly, via activation of the PI3K/AKT/mTOR signaling pathway. 相似文献
4.
5.
6.
Mengmeng Zhuang Yuequ Deng Wenwen Zhang Bo Zhu Hao Yan Jiaqi Lou Pan Zhang Qingwei Cui Hao Tang Han Sun Yong Sun 《Cell death & disease》2021,12(6)
Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.Subject terms: Cell growth, Cell migration 相似文献
7.
8.
Yihao Yang Ziyan Shen Youguang Li Chenda Xu Han Xia Hao Zhuang Shengyuan Sun Min Guo Changjie Yan 《植物学报(英文版)》2022,64(10):1860-1865
Rice eating and cooking quality (ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content (GPC) is negatively related to ECQ, making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein glutelin rapidly produced lines with downregulated GPC and improved ECQ. Our finding provides a new strategy for improving rice ECQ. 相似文献
9.
Circulating miRNAs are promising biomarkers for predicting the aggressiveness of hepatocellular carcinoma (HCC). We aimed to identify differentially expressed miRNAs in the serum of HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stage, and to investigate the potential of serum miRNAs as biomarkers for patient outcomes. In the discovery stage, TaqMan Low-Density Array was used to test the difference in levels of serum miRNAs between 20 patients with portal vein tumor thrombosis (PVTT) and 20 patients without PVTT. The detected serum miRNAs then were validated in 182 patients. Fifteen serum miRNAs showed more than two-fold higher expression in patients with PVTT, and miR-128-2 was found to be significantly up-regulated and was selected for further validation. In the validation stage, patients were divided into two groups with low or high serum miR-128-2 using the median expression level of all 182 cases as the cut-off point. Kaplan-Meier analysis revealed that patients with low level of serum miR-128-2 had favorable trends of survival (log rank = 13.031, p < 0.001). The median survivals for patients with a low and high level of serum miR-128-2 were 625 (95% CI, 527–722) days and 426 (95% CI, 362–491) days, respectively. MiR-128-2 was also an independent factor of overall survival (p = 0.001, HR 2.793, 95%CI 1.550, 5.033). Serum levels of the ubiquitously expressed miR-128-2 showed no significant correlation with parameters of liver damage or liver function. In addition, expressions of miR-128-2 in HCC tissues were up-regulated in comparison with adjacent non-tumor tissues. In conclusion, serum level of miR-128-2 serves as a noninvasive biomarker for the overall survival of patients with hepatocellular carcinoma. 相似文献
10.