全文获取类型
收费全文 | 17584篇 |
免费 | 1831篇 |
国内免费 | 1785篇 |
出版年
2024年 | 43篇 |
2023年 | 230篇 |
2022年 | 547篇 |
2021年 | 977篇 |
2020年 | 708篇 |
2019年 | 900篇 |
2018年 | 886篇 |
2017年 | 656篇 |
2016年 | 849篇 |
2015年 | 1103篇 |
2014年 | 1329篇 |
2013年 | 1364篇 |
2012年 | 1585篇 |
2011年 | 1448篇 |
2010年 | 882篇 |
2009年 | 835篇 |
2008年 | 880篇 |
2007年 | 792篇 |
2006年 | 629篇 |
2005年 | 571篇 |
2004年 | 599篇 |
2003年 | 625篇 |
2002年 | 559篇 |
2001年 | 462篇 |
2000年 | 349篇 |
1999年 | 293篇 |
1998年 | 184篇 |
1997年 | 137篇 |
1996年 | 143篇 |
1995年 | 91篇 |
1994年 | 91篇 |
1993年 | 73篇 |
1992年 | 71篇 |
1991年 | 74篇 |
1990年 | 56篇 |
1989年 | 39篇 |
1988年 | 30篇 |
1987年 | 30篇 |
1986年 | 21篇 |
1985年 | 29篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 750 毫秒
891.
Shiqing Liu Chengping Hu Min Li Jian An Wolong Zhou Jia Guo Yao Xiao 《Cell death & disease》2022,13(1)
Lung cancer is one of the most lethal malignant tumors in the world. The high recurrence and mortality rate make it urgent for scientists and clinicians to find new targets for better treatment of lung cancer. Early studies indicated that estrogen receptor β (ERβ) might impact the progression of non-small-cell lung cancer (NSCLC). However, the detailed mechanisms, especially its linkage to the CXCR4-mediated cell invasion, remain unclear. Here we found that ERβ could promote NSCLC cell invasion via increasing the circular RNA (circRNA), circ-TMX4, expression via directly binding to the 5′ promoter region of its host gene TMX4. ERβ-promoted circ-TMX4 could then sponge and inhibit the micro RNA (miRNA, miR), miR-622, expression, which can then result in increasing the CXCR4 messenger RNA translation via a reduced miRNA binding to its 3′ untranslated region (3′UTR). The preclinical study using an in vivo mouse model with orthotopic xenografts of NSCLC cells confirmed the in vitro data, and the human NSCLC database analysis and tissue staining also confirmed the linkage of ERβ/miR-622/CXCR4 signaling to the NSCLC progression. Together, our findings suggest that ERβ can promote NSCLC cell invasion via altering the ERβ/circ-TMX4/miR-622/CXCR4 signaling, and targeting this newly circ-TMX4/miR-622/CXCR4 signaling may help us find new treatment strategies to better suppress NSCLC progression.Subject terms: Non-small-cell lung cancer, Metastasis 相似文献
892.
Xiao-Yu Geng Ming-Ke Wang Jin-Hong Chen Liang Xiao Ji-Shun Yang 《World journal of biological chemistry》2023,14(1):1-12
The marine environment can be extremely dangerous, and the harm caused by marine organisms when they contact the human body can be especially harmful, even deadly. Contact includes stings, bites, wounds, and consumption as food. In this article, the characteristics of the common marine biological injuries are summarized, the major marine organisms causing damage in China’s marine waters are described, and injury prevention and treatment methods are discussed. 相似文献
893.
Zirui Liu Yiquan Li Yilong Zhu Nan Li Wenjie Li Chao Shang Gaojie Song Shanzhi Li Jianan Cong Tingyu Li Zhiru Xiu Jing Lu Chenchen Ge Xia Yang Yaru Li Lili Sun Xiao Li Ningyi Jin 《International journal of biological sciences》2022,18(2):717
Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy. 相似文献
894.
895.
Shuai Fan Guangxin Lv Xiao Feng Guangteng Wu Yuanyuan Jin Maocai Yan Zhaoyong Yang 《The Journal of biological chemistry》2022,298(2)
The potential antimicrobial compound Chuangxinmycin (CXM) targets the tryptophanyl-tRNA synthetase (TrpRS) of both Gram-negative and Gram-positive bacteria. However, the specific steric recognition mode and interaction mechanism between CXM and TrpRS is unclear. Here, we studied this interaction using recombinant GsTrpRS from Geobacillus stearothermophilus by X-ray crystallography and molecular dynamics (MD) simulations. The crystal structure of the recombinant GsTrpRS in complex with CXM was experimentally determined to a resolution at 2.06 Å. After analysis using a complex-structure probe, MD simulations, and site-directed mutation verification through isothermal titration calorimetry, the interaction between CXM and GsTrpRS was determined to involve the key residues M129, D132, I133, and V141 of GsTrpRS. We further evaluated binding affinities between GsTrpRS WT/mutants and CXM; GsTrpRS was found to bind CXM through hydrogen bonds with D132 and hydrophobic interactions between the lipophilic tricyclic ring of CXM and M129, I133, and V141 in the substrate-binding pockets. This study elucidates the precise interaction mechanism between CXM and its target GsTrpRS at the molecular level and provides a theoretical foundation and guidance for the screening and rational design of more effective CXM analogs against both Gram-negative and Gram-positive bacteria. 相似文献
896.
897.
898.
Xiaohu Li Xin Zhang Inam
Ullah Khan Nina
N. Guo Bing Wang Yifeng Guo Bufan Xiao Yueshan Zhang Yimin Chu Junsong Chen Fang Guo 《Bioscience reports》2022,42(2)
Background: Breast cancer is the main lethal disease among females. The combination of lobaplatin and microwave hyperthermia plays a crucial role in several kinds of cancer in the clinic, but its possible mechanism in breast cancer has remained indistinct.Methods: Mouse models were used to detect breast cancer progression. Cell growth was explored with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphonyl)-2H-tetrazolium) and colony formation assays. Cell migration and invasion were investigated with a transwell assay. Cell apoptosis was probed with flow cytometry. The expression of apoptosis-associated proteins was examined with Western blots.Result: Combination treatment decreased breast cancer cell viability, colony formation, cell invasion and metastasis. In addition, the treatment-induced breast cancer cell apoptosis and autophagy, activated the c-Jun N-terminal kinase (JNK) signaling pathway, suppressed the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and down-regulated IAP and Bcl-2 family protein expression.Conclusion: These results indicate that lobaplatin is an effective breast cancer anti-tumor agent. Microwave hyperthermia was a useful adjunctive treatment. Combination treatment was more efficient than any single therapy. The possible mechanism for this effect was mainly associated with activation of the JNK signaling pathway, inactivation of the AKT/mTOR signaling pathway and down-regulation of the Bcl-2 and IAP families. 相似文献
899.