全文获取类型
收费全文 | 398篇 |
免费 | 41篇 |
国内免费 | 81篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 14篇 |
2020年 | 15篇 |
2019年 | 10篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 11篇 |
2015年 | 33篇 |
2014年 | 38篇 |
2013年 | 39篇 |
2012年 | 43篇 |
2011年 | 38篇 |
2010年 | 16篇 |
2009年 | 22篇 |
2008年 | 20篇 |
2007年 | 26篇 |
2006年 | 31篇 |
2005年 | 21篇 |
2004年 | 19篇 |
2003年 | 13篇 |
2002年 | 23篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
排序方式: 共有520条查询结果,搜索用时 234 毫秒
511.
512.
Hong Chen Chenghong Zheng Xin ZhangJianshuang Li Jiong LiLing Zheng Kun Huang 《Peptides》2011,32(8):1634-1639
Apelin, a newly identified bioactive adipokine, has been found to play important roles in multiple diseases, including diabetes, hypertension and cardiovascular diseases with unclear molecular mechanisms. The present study aimed to investigate the effects of apelin on endoplasmic reticulum (ER) stress in the pancreas of Akita mice, a well-established type 1 diabetic model. Apelin-13 (400 pmol/kg) was injected from tail vein for 10 weeks. The physiological characters of experimental animals were evaluated, pancreatic islet morphology and insulin content were assessed by immunohistochemistry, and ER stress markers in the pancreas were examined by Western blots. Our results indicate apelin treatment significantly ameliorates diabetes-induced reduction in pancreatic islet mass and insulin content. Further studies suggested apelin treatment alleviates ER stress by inhibiting the diabetes induced up-regulation of PERK and IRE1α and chaperones (GRP78, calnexin and Hsp70) levels in Akita mice. We also demonstrated that apelin treatment normalizes the diabetes induced alteration of AKT and ERK activations in the pancreas of Akita mice. Taken together, these results suggest a novel physiological role of apelin in alleviating ER stress in the pancreas of type 1 diabetes. 相似文献
513.
Peng Deng Quan Yuan Yingduan Cheng Jiong Li Zhenqing Liu Yan Liu Ye Li Trent Su Jing Wang Mari Ekimyan Salvo Weiguang Wang Guoping Fan Karen Lyons Bo Yu Cun-Yu Wang 《Cell Stem Cell》2021,28(6):1057-1073.e7
- Download : Download high-res image (161KB)
- Download : Download full-size image
514.
Mengmeng Liu Guohong Li Mengli Wang Xinran Cheng Yinxue Huang Mingrui Xu Kaikai Li Jiong Chen Xiaoyan Zhu Shanting Zhao 《Journal of molecular histology》2018,49(5):519-530
During the development of mammalian cortex, late neurons generated by neuronal progenitors bypass earlier-born neurons and migrate to reach upper layers of cortical plate in an inner-to-outer fashion. Filamentous-actin (F-actin) can regulate neuronal migration, whereas Coactosin-like protein 1 (Cotl1) modulates F-actin. Lys 75 and Arg 73 of Cotl1 play an important role in binding F-actin; when they are mutated to Glu, Cotl1 cannot bind F-actin, called as a non-actin-binding mutant (ABM). The Lys 131 site of Cotl1, the 5-Lipoxygenase (5LO) binding site, is spatially close to Lys 75, leading to impact the binding of Cotl1 to F-actin. When Lys 131 is mutated to Ala (K131A), Cotl1 cannot bind to 5LO. We have demonstrated that overexpression of Cotl1 inhibited neuronal migration and increased the length of neuronal leading processes. To further explore cellular and molecular mechanisms of Cotl1’s effect on neuronal migration, we constructed two mutant vectors—Cotl1-ABM and Cotl1-K131A and studied using in utero electroporation and primary neuronal culture technique. Results indicated that in the Cotl1-ABM group, the neuronal migration and length of the leading process both recovered as control neurons at the postnatal day 1 (P1), while in the Cotl1-K131A group, numerous neurons remained in deeper layers of cortical plate or intermediate zone. However, at P7, most Cotl1-K131A transfected neurons reached their destination. Moreover, we found that overexpression of Cotl1 inhibited the proliferation and mitotic activity of NPs. Therefore, These results demonstrated that Cotl1 played an important role in mouse neocortical development. 相似文献
515.
516.
Bo-Duan Xiao Yu-Jia Zhao Xiao-Yuan Jia Jiong Wu Yi-Gang Wang Fang Huang 《World journal of stem cells》2020,12(6):481-487
Cancer cells possess metabolic properties that are different from those of benign cells. p21, encoded by CDKN1A gene, also named p21Cip1/WAF1, was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. CDKN1A (p21) acts as the downstream target gene of TP53 (p53), and its expression is induced by wild-type p53 and it is not associated with mutant p53. p21 has been characterized as a vital regulator that involves multiple cell functions, including G1/S cell cycle progression, cell growth, DNA damage, and cell stemness. In 1994, p21 was found as a tumor suppressor in brain, lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways. In addition, expression of p21 is closely related to the resting state or terminal differentiation of cells. p21 is also associated with cancer stem cells and acts as a biomarker for such cells. In cancer therapy, given the importance of p21 in regulating the G1/S and G2 check points, it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy. 相似文献
517.
Guan-Man Li Lei Li Meng-Qing Li Xu Chen Qiao Su Zhi-Juan Deng Hai-Bo Liu Bin Li Wen-Hui Zhang Yong-Xu Jia Wen-Jian Wang Jie-Yi Ma Hai-Liang Zhang Dan Xie Xiao-Feng Zhu Yu-Long He Xin-Yuan Guan Jiong Bi 《Cell death and differentiation》2021,28(3):952
Dysregulation of the balance between cell proliferation and cell death is a central feature of malignances. Death-associated protein kinase 3 (DAPK3) regulates programmed cell death including apoptosis and autophagy. Our previous study showed that DAPK3 downregulation was detected in more than half of gastric cancers (GCs), which was related to tumor invasion, metastasis, and poor prognosis. However, the precise molecular mechanism underlying DAPK3-mediated tumor suppression remains unclear. Here, we showed that the tumor suppressive function of DAPK3 was dependent on autophagy process. Mass spectrometry, in vitro kinase assay, and immunoprecipitation revealed that DAPK3 increased ULK1 activity by direct ULK1 phosphorylation at Ser556. ULK1 phosphorylation by DAPK3 facilitates the ULK1 complex formation, the VPS34 complex activation, and autophagy induction upon starvation. The kinase activity of DAPK3 and ULK1 Ser556 phosphorylation were required for DAPK3-modulated tumor suppression. The coordinate expression of DAPK3 with ULK1 Ser556 phosphorylation was confirmed in clinical GC samples, and this co-expression was correlated with favorable survival outcomes in patients. Collectively, these findings indicate that the tumor-suppressor roles of DAPK3 in GC are associated with autophagy and that DAPK3 is a novel autophagy regulator, which can directly phosphorylate ULK1 and activate ULK1. Thus, DAPK3 might be a promising prognostic autophagy-associated marker.Subject terms: Tumour-suppressor proteins, Macroautophagy 相似文献
518.
Baoju Wang Longfang Yao Yueyue Jing Yiyan Fei Qianming Bai Lan Mi Jiong Ma 《Journal of biophotonics》2020,13(5)
Either modulated illumination or temporal fluctuation analysis can assist super‐resolution techniques in overcoming the diffraction limit of conventional optical microscopy. As they are not contradictory to each other, an effective combination of spatial and temporal super‐resolution mechanisms would further improve the resolution of fluorescent images. Here, a super‐resolution imaging method called fluctuation‐enhanced Airyscan technology (FEAST) is proposed, which achieves ~40 nm lateral imaging resolution and is useful for a range of fluorescent proteins and organic dyes. It was demonstrated not only to obtain different subcellular super‐resolution images, but also to improve the accuracy of counting the average human epidermal growth factor receptor 2 (HER2) copy number for diagnosis in breast cancer. Furthermore, the combination of FEAST and sample expansion microscopy (Ex‐FEAST) improves the lateral resolution to ~26 nm. 相似文献
519.
正Intensive aquaculture has increased the severity and frequency of fish diseases. Given the functional importance of gut microbiota in various facets of host physiology, modulation of this microbiota is a feasible strategy to mitigate emerging diseases in aquaculture. To achieve this, a fundamental understanding of the interplay among fish health, microbiota,and invading pathogens is required. This commentary focuses on current knowledge regarding the associations between fish diseases, dysbiosis of gut microbiota, and immune responses.Furthermore, updated research on fish disease from an ecological perspective is discussed, including colonization 相似文献
520.