全文获取类型
收费全文 | 3647篇 |
免费 | 293篇 |
国内免费 | 210篇 |
出版年
2024年 | 9篇 |
2023年 | 99篇 |
2022年 | 91篇 |
2021年 | 340篇 |
2020年 | 390篇 |
2019年 | 666篇 |
2018年 | 168篇 |
2017年 | 105篇 |
2016年 | 107篇 |
2015年 | 112篇 |
2014年 | 289篇 |
2013年 | 281篇 |
2012年 | 163篇 |
2011年 | 159篇 |
2010年 | 112篇 |
2009年 | 114篇 |
2008年 | 94篇 |
2007年 | 94篇 |
2006年 | 79篇 |
2005年 | 77篇 |
2004年 | 75篇 |
2003年 | 69篇 |
2002年 | 69篇 |
2001年 | 28篇 |
2000年 | 52篇 |
1999年 | 38篇 |
1998年 | 25篇 |
1997年 | 19篇 |
1996年 | 20篇 |
1995年 | 18篇 |
1994年 | 12篇 |
1993年 | 6篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 10篇 |
1978年 | 10篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 14篇 |
1974年 | 4篇 |
1973年 | 5篇 |
排序方式: 共有4150条查询结果,搜索用时 46 毫秒
71.
72.
JiHoon Kang EunGi Kim Wanyeon Kim Ki Moon Seong HyeSook Youn Jung Woo Kim Joon Kim BuHyun Youn 《The Journal of biological chemistry》2013,288(38):27343-27357
Radioresistance is a major cause of decreasing the efficiency of radiotherapy for non-small cell lung cancer (NSCLC). To understand the radioresistance mechanisms in NSCLC, we focused on the radiation-induced Notch-1 signaling pathway involved in critical cell fate decisions by modulating cell proliferation. In this study, we investigated the use of Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity in NSCLC cells, NCI-H1299 and NCI-H460, with different levels of radioresistance. Rhamnetin and cirsiliol were selected as candidate Notch-1-regulating radiosensitizers based on the results of assay screening for activity and pharmacological properties. Treatment with rhamnetin or cirsiliol reduced the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression. Indeed, rhamnetin and cirsiliol increased the expression of tumor-suppressive microRNA, miR-34a, in a p53-dependent manner, leading to inhibition of Notch-1 expression. Consequently, reduced Notch-1 expression promoted apoptosis through significant down-regulation of the nuclear factor-κB pathway, resulting in a radiosensitizing effect on NSCLC cells. Irradiation-induced epithelial-mesenchymal transition was also notably attenuated in the presence of rhamnetin and cirsiliol. Moreover, an in vivo xenograft mouse model confirmed the radiosensitizing and epithelial-mesenchymal transition inhibition effects of rhamnetin and cirsiliol we observed in vitro. In these mice, tumor volume was significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone. Taken together, our findings provided evidence that rhamnetin and cirsiliol can act as promising radiosensitizers that enhance the radiotherapeutic efficacy by inhibiting radiation-induced Notch-1 signaling associated with radioresistance possibly via miR-34a-mediated pathways. 相似文献
73.
74.
75.
L Xiaoping Y Zhibin L Wenjuan W Zeyou X Gang L Zhaohui Z Ying W Minghua L Guiyuan 《Cell death & disease》2013,4(6):e675
Epigenetic mechanisms have important roles in carcinogenesis. We certified that the mRNA translation-related gene cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is hypomethylated and overexpressed in glioma cells and tissues. The knockdown of CPEB1 reduced cell senescence by regulating the expression or distribution of p53 in glioma cells. CPEB1 is also regulated directly by the tumor suppressor miR-101, a potential marker of glioma. It is known that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) are direct targets of miR-101. We demonstrated that miR-101 downregulated the expression of CPEB1 through reversing the methylation status of the CPEB1 promoter by regulating the presence on the promoter of the methylation-related histones H3K4me2, H3K27me3, H3K9me3 and H4K20me3. The epigenetic regulation of H3K27me3 on CPEB1 promoter is mediated by EZH2 and EED. EZH2 has a role in the regulation of H3K4me2. Furthermore, the downregulation of CPEB1 induced senescence in a p53-dependent manner. 相似文献
76.
77.
78.
79.
《Journal of receptor and signal transduction research》2013,33(5):338-341
AbstractMicroRNAs exert their biologic effects by targeting specific mRNAs for degradation or translational inhibition. MicroRNA-mediated regulation is complex, potentially affecting expression of the host gene, related enzymes within the same pathway or apparently distinct targets. miR-107 is found to be implicated in the pathogenesis of some diseases. This review was performed to sum up the role of miR-107 and its signaling pathways in renal diseases. 相似文献
80.