全文获取类型
收费全文 | 6618篇 |
免费 | 640篇 |
国内免费 | 748篇 |
出版年
2024年 | 18篇 |
2023年 | 105篇 |
2022年 | 190篇 |
2021年 | 370篇 |
2020年 | 282篇 |
2019年 | 340篇 |
2018年 | 330篇 |
2017年 | 253篇 |
2016年 | 317篇 |
2015年 | 472篇 |
2014年 | 540篇 |
2013年 | 521篇 |
2012年 | 670篇 |
2011年 | 548篇 |
2010年 | 340篇 |
2009年 | 352篇 |
2008年 | 342篇 |
2007年 | 315篇 |
2006年 | 233篇 |
2005年 | 242篇 |
2004年 | 226篇 |
2003年 | 182篇 |
2002年 | 157篇 |
2001年 | 118篇 |
2000年 | 97篇 |
1999年 | 80篇 |
1998年 | 61篇 |
1997年 | 53篇 |
1996年 | 40篇 |
1995年 | 32篇 |
1994年 | 34篇 |
1993年 | 21篇 |
1992年 | 30篇 |
1991年 | 30篇 |
1990年 | 11篇 |
1989年 | 12篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 1篇 |
排序方式: 共有8006条查询结果,搜索用时 31 毫秒
51.
Jia-Qing Zhang Bin-Wen Gao Jing Wang Xian-Wei Wang Qiao-Ling Ren Jun-Feng Chen Qiang Ma Bao-song Xing 《PloS one》2016,11(1)
Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. 相似文献
52.
53.
54.
Xiaoqun Peng Menglong Wang Yiqi Li Wei Yan Zhenyi Chang Zhufeng Chen Chunjue Xu Chengwei Yang Xing Wang Deng Jianxin Wu Xiaoyan Tang 《植物学报(英文版)》2020,62(8):1227-1245
Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane‐localized legume‐lectin receptor kinase that we named OsLecRK‐S.7. OsLecRK‐S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK‐S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376, Ser378, Thr386, Thr403, and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk‐s.7 mutant plant overexpressing OsLecRK‐S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK‐S.7 was a key regulator of pollen development. 相似文献
55.
Songyu Tian Wanqi Mi Mingyue Zhang Linan Xing Chunlong Zhang 《Journal of cellular and molecular medicine》2020,24(4):2582-2592
Ovarian cancer (OvCa) causes the highest mortality among all gynaecologic cancers. A large number of mRNA‐ or miRNA‐based signatures were identified for OvCa patient prognosis. However, the comprehensive analysis of function‐level prognostic signatures is currently not considered in OvCa. In the present study, we respectively inferred subpathway activities from mRNA and miRNA levels based on high‐throughput expression profiles and reconstructed subpathways. Firstly, the activities of two tumour pathways were calculated and the difference between normal and tumour samples were analysed using multiple tumour types. Then, we calculated subpathway activities for OvCa based on the expression profiles from both mRNA and miRNA levels. Furthermore, based on these subpathway activity matrices, we performed bootstrap analysis to obtain sub‐training sets and utilized univariate method to identify robust OvCa prognostic subpathways. A comprehensive comparison of subpathway results between these two levels was performed. As a result, we observed subpathway mutual exclusion trend between the levels of mRNA and miRNA, which indicated the necessary of combining mRNA‐miRNA levels. Finally, by using ICGC data as testing sets, we utilized two strategies to verify survival predictive power of the mRNA‐miRNA combined subpathway signatures and performed comparisons with results from individual levels. It was confirmed that our framework displayed application to identify robust and efficient prognostic signatures for OvCa, and the combined signatures indeed exhibited advantages over individual ones. In the study, we took a step forward in relevant novel integrated functional signatures for OvCa prognosis. 相似文献
56.
Yunhong Tian Yunming Tian Yinuo Tu Guoqian Zhang Xing Zeng Jie Lin Meiling Ai Zixu Mao Ronghui Zheng Yawei Yuan 《Journal of cellular and molecular medicine》2020,24(17):9533-9544
Cancer stem cells (CSCs) are a source of tumour recurrence in patients with nasopharyngeal carcinoma (NPC); however, the function of microRNA‐124 (miR‐124) in NPC CSCs has not been clearly defined. In this study, we investigated the role of miR‐124 in NPC CSCs. qRT‐PCR was performed to measure miR‐124 expression in NPC tissues and cell lines and the effects of miR‐124 on stem‐like properties and radiosensitivity of NPC cells measured. Luciferase reporter assays and rescue experiments were used to investigate the interaction of miR‐124 with the 3′UTR of junctional adhesion molecule A (JAMA). Finally, we examined the effects of miR‐124 in an animal model and clinical samples. Down‐regulation of miR‐124 was detected in cancer tissues and was inversely associated with tumour stage and lymph node metastasis. Overexpression of miR‐124 inhibited stemness properties and enhanced radiosensitivity of NPC cells in vitro and in vivo via targeting JAMA. Up‐regulation of miR‐124 was correlated with superior overall survival of patients with NPC. Our study demonstrates that miR‐124 can inhibit stem‐like properties and enhance radiosensitivity by directly targeting JAMA in NPC. These findings provide novel insights into the molecular mechanisms underlying therapy failure in NPC. 相似文献
57.
Chen Zhixia Yu Xiuli Zhang Aiying Wang Fangfang Xing Yankun 《International journal of peptide research and therapeutics》2020,26(4):1711-1719
International Journal of Peptide Research and Therapeutics - Most existing antimicrobial peptides (AMPs) are α-helical and cationic that exhibit typical amphipathic feature to facilitate... 相似文献
58.
Chunyu Li Yongping Chen Xueping Chen Qianqian Wei Ruwei Ou Xiaojing Gu Bei Cao Huifang Shang 《Journal of cellular and molecular medicine》2020,24(15):8614-8622
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. A fundamental pathogenesis of ALS is the prolonged cell stress in neurons, which is caused by either accumulation of protein aggregates or reactive oxygen species. However, the mechanistic link between stress sensing and cell death is unsettled. Here, we identify that miR‐183‐5p, a neuron‐enriched miRNA, couples stress sensing and cell death programming in ALS. miR‐183‐5p is immediately induced by hydrogen peroxide, tunicamycin or TNF‐α in neurons. The overexpression of miR‐183‐5p increases neuron survival under stress conditions, whereas its knockdown causes neuron death. miR‐183‐5p coordinates apoptosis and necroptosis pathways by directly targeting PDCD4 and RIPK3, and thus protects neurons against cell death under stress conditions. The consistent reduction of miR‐183‐5p in ALS patients and mouse models enhances the notion that miR‐183‐5p is a central regulator of motor neuron survival under stress conditions. Our study supplements current understanding of the mechanistic link between cell stress and death/survival, and provides novel targets for clinical interventions of ALS. 相似文献
59.
Shenglong Li Yi Pei Wei Wang Fei Liu Ke Zheng Xiaojing Zhang 《Journal of cellular and molecular medicine》2020,24(3):2202-2214
Under the microenvironment, tumour progression is substantially affected by cell‐cell communication. In spite of the mediating effect of extracellular nanovesicles (EVs) on cell‐cell communication by packaging into circRNAs, the effect of EVs circRNA hsa_circ_0000190 (circ‐0000190) in osteosarcoma is still not clear. Circ‐0000190 expressions in tissues and EVs from plasma were compared between osteosarcoma patients and controls. Thereafter, receiver operating characteristic (ROC) curve was drawn and area under the curve was calculated to examine whether the diagnostic results were accurate, and the effect of EVs circ‐0000190 was dug out via the determination of cell phenotypes and animal assays. Results showed circ‐0000190 exhibited an obvious reduction in EVs and tissues of osteosarcoma patients (P < .05). It was also discovered that EVs encapsulated the majority of circ‐0000190, and EVs‐encapsulated circ‐0000190 could be applied to make a distinction between osteosarcoma patients and controls. Besides, EVs circ‐0000190 in osteosarcoma cells transported from normal cells weakened the capacities of osteosarcoma cells to migrate, proliferate and invade, so as to block their biological malignant behaviours (P < .05). In addition, under the action of EVs circ‐0000190, tumour growth was impeded and the expression of TET1 was inhibited via the competitive binding to miR‐767‐5p. In all, EVs circ‐0000190 has a good prospect as it can be regarded as a new biomarker for detecting osteosarcoma. EVs circ‐0000190 transported from normal cells to osteosarcoma cells impeded the in vitro and in vivo development of osteosarcoma, implying that EVs circ‐0000190 exerts an effect on communication between normal cells and osteosarcoma cells in the carcinogenesis process of osteosarcoma. 相似文献
60.
Xiaohong Gu Yuechun Li Kaixin Chen Xingang Wang Zhongyu Wang Hao Lian Yuanzheng Lin Xing Rong Maoping Chu Jiafeng Lin Xiaoling Guo 《Journal of cellular and molecular medicine》2020,24(13):7515-7530
Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future. 相似文献