全文获取类型
收费全文 | 19484篇 |
免费 | 1457篇 |
国内免费 | 1336篇 |
出版年
2024年 | 53篇 |
2023年 | 291篇 |
2022年 | 629篇 |
2021年 | 1068篇 |
2020年 | 711篇 |
2019年 | 893篇 |
2018年 | 805篇 |
2017年 | 616篇 |
2016年 | 884篇 |
2015年 | 1255篇 |
2014年 | 1478篇 |
2013年 | 1510篇 |
2012年 | 1757篇 |
2011年 | 1532篇 |
2010年 | 957篇 |
2009年 | 818篇 |
2008年 | 955篇 |
2007年 | 769篇 |
2006年 | 734篇 |
2005年 | 579篇 |
2004年 | 531篇 |
2003年 | 472篇 |
2002年 | 410篇 |
2001年 | 374篇 |
2000年 | 342篇 |
1999年 | 316篇 |
1998年 | 206篇 |
1997年 | 190篇 |
1996年 | 175篇 |
1995年 | 152篇 |
1994年 | 116篇 |
1993年 | 106篇 |
1992年 | 132篇 |
1991年 | 110篇 |
1990年 | 96篇 |
1989年 | 58篇 |
1988年 | 46篇 |
1987年 | 49篇 |
1986年 | 26篇 |
1985年 | 26篇 |
1984年 | 16篇 |
1983年 | 20篇 |
1982年 | 4篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
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
992.
993.
Yi-Chin Candace Tsai Lynette Liew Zhijun Guo Di Liu Oliver Mueller-Cajar 《The Journal of biological chemistry》2022,298(1)
The CO2-fixing enzyme rubisco is responsible for almost all carbon fixation. This process frequently requires rubisco activase (Rca) machinery, which couples ATP hydrolysis to the removal of inhibitory sugar phosphates, including the rubisco substrate ribulose 1,5-bisphosphate (RuBP). Rubisco is sometimes compartmentalized in carboxysomes, bacterial microcompartments that enable a carbon dioxide concentrating mechanism (CCM). Characterized carboxysomal rubiscos, however, are not prone to inhibition, and often no activase machinery is associated with these enzymes. Here, we characterize two carboxysomal rubiscos of the form IAC clade that are associated with CbbQO-type Rcas. These enzymes release RuBP at a much lower rate than the canonical carboxysomal rubisco from Synechococcus PCC6301. We found that CbbQO-type Rcas encoded in carboxysome gene clusters can remove RuBP and the tight-binding transition state analog carboxy-arabinitol 1,5-bisphosphate from cognate rubiscos. The Acidithiobacillus ferrooxidans genome encodes two form IA rubiscos associated with two sets of cbbQ and cbbO genes. We show that the two CbbQO activase systems display specificity for the rubisco enzyme encoded in the same gene cluster, and this property can be switched by substituting the C-terminal three residues of the large subunit. Our findings indicate that the kinetic and inhibitory properties of proteobacterial form IA rubiscos are diverse and predict that Rcas may be necessary for some α-carboxysomal CCMs. These findings will have implications for efforts aiming to introduce biophysical CCMs into plants and other hosts for improvement of carbon fixation of crops. 相似文献
994.
995.
996.
997.
998.
Xiaoman Li Liang Wang Jialin Hao Qingfeng Zhu Min Guo Changjing Wu Sihui Li Qiqiang Guo Qiuhong Ren Ning Bai Fei Yi Bo Jiang Wenyu Zhang Yanling Feng Hongde Xu Han Jiang Xiaoyue Zhai Guohua Zhang Hong-long Ji Xuesong Yang Dan Zhang Jianhua Fu Jianjun Chang Xiaoyu Song Liu Cao 《International journal of biological sciences》2022,18(3):1107
The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood. 相似文献
999.
1000.
Wenna Guo Shanshan Ma Yanting Zhang Hongtao Liu Ya Li JiTian Xu Bo Yang Fangxia Guan 《Journal of cellular and molecular medicine》2022,26(2):449
Glioma is the most malignant and aggressive type of brain tumour with high heterogeneity and mortality. Although some clinicopathological factors have been identified as prognostic biomarkers, the individual variants and risk stratification in patients with lower grade glioma (LGG) have not been fully elucidated. The primary aim of this study was to identify an efficient DNA methylation combination biomarker for risk stratification and prognosis in LGG. We conducted a retrospective cohort study by analysing whole genome DNA methylation data of 646 patients with LGG from the TCGA and GEO database. Cox proportional hazard analysis was carried out to screen and construct biomarker model that predicted overall survival (OS). The Kaplan‐Meier survival curves and time‐dependent ROC were constructed to prove the efficiency of the signature. Then, another independent cohort was used to further validate the finding. A two‐CpG site DNA methylation signature was identified by multivariate Cox proportional hazard analysis. Further analysis indicated that the signature was an independent survival predictor from other clinical factors and exhibited higher predictive accuracy compared with known biomarkers. This signature was significantly correlated with immune‐checkpoint blockade, immunotherapy‐related signatures and ferroptosis regulator genes. The expression pattern and functional analysis showed that these two genes corresponding with two methylation sites contained in the model were correlated with immune infiltration level, and involved in MAPK and Rap1 signalling pathway. The signature may contribute to improve the risk stratification of patients and provide a more accurate assessment for precision medicine in the clinic. 相似文献