全文获取类型
收费全文 | 18780篇 |
免费 | 1703篇 |
国内免费 | 1408篇 |
出版年
2023年 | 209篇 |
2022年 | 525篇 |
2021年 | 889篇 |
2020年 | 603篇 |
2019年 | 687篇 |
2018年 | 726篇 |
2017年 | 538篇 |
2016年 | 699篇 |
2015年 | 1147篇 |
2014年 | 1263篇 |
2013年 | 1364篇 |
2012年 | 1561篇 |
2011年 | 1498篇 |
2010年 | 980篇 |
2009年 | 833篇 |
2008年 | 905篇 |
2007年 | 875篇 |
2006年 | 770篇 |
2005年 | 656篇 |
2004年 | 617篇 |
2003年 | 543篇 |
2002年 | 515篇 |
2001年 | 392篇 |
2000年 | 390篇 |
1999年 | 359篇 |
1998年 | 169篇 |
1997年 | 161篇 |
1996年 | 158篇 |
1995年 | 119篇 |
1994年 | 146篇 |
1993年 | 90篇 |
1992年 | 155篇 |
1991年 | 147篇 |
1990年 | 122篇 |
1989年 | 98篇 |
1988年 | 82篇 |
1987年 | 96篇 |
1986年 | 83篇 |
1985年 | 92篇 |
1984年 | 48篇 |
1983年 | 48篇 |
1982年 | 48篇 |
1981年 | 36篇 |
1980年 | 37篇 |
1979年 | 52篇 |
1978年 | 41篇 |
1977年 | 45篇 |
1976年 | 33篇 |
1975年 | 35篇 |
1974年 | 44篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
Lin Li Yaping Zhang Wanzhi Ma Hui Chen Mengqin Liu Ran An Bingxiao Cheng Xingguo Liang 《Nucleic acids research》2022,50(2):684
In vivo, left-handed DNA duplex (usually refers to Z-DNA) is mainly formed in the region of DNA with alternating purine pyrimidine (APP) sequence and plays significant biological roles. It is well known that d(CG)n sequence can form Z-DNA most easily under negative supercoil conditions, but its essence has not been well clarified. The study on sequence dependence of Z-DNA stability is very difficult without modification or inducers. Here, by the strong topological constraint caused by hybridization of two complementary short circular ssDNAs, left-handed duplex part was generated for various sequences, and their characteristics were investigated by using gel-shift after binding to specific proteins, CD and Tm analysis, and restriction enzyme cleavage. Under the strong topological constraint, non-APP sequences can also form left-handed DNA duplex as stable as that of APP sequences. As compared with non-APP sequences, the thermal stability difference for APP sequences between Z-form and B-form is smaller, which may be the reason that Z-DNA forms preferentially for APP ones. This result can help us to understand why nature selected APP sequences to regulate gene expression by transient Z-DNA formation, as well as why polymer with chirality can usually form both duplexes with left- or right-handed helix. 相似文献
942.
943.
Yuting Zhang Hongxia Gao Xiaohui Hu Qisheng Wang Fanglin Zhong Xuelan Zhou Cheng Lin Yang Yang Junkang Wei Weian Du Huaiqiu Huang Huan Zhou Wei He Hua Zhang Yuting Zhang Peter J. McCormick Jinheng Fu Dan Wang Yang Fu Xiaolu Lu Tengfei Zhang Jingjing Duan Bingjie Qin Haihai Jiang Jun Luo Yan Zhang Qi Chen Qunfeng Luo Lin Cheng Zheng Zhang Jin Zhang Jian Li 《Journal of virology》2022,96(1)
944.
945.
946.
Lei Wu Xiaolu Jiao Dezhi Zhang Yalin Cheng Gang Song Yanhua Qu Fumin Lei 《Current Genomics》2021,22(7):496
Genomic data are important for understanding the origin and evolution of traits. Under the context of rapidly developing of sequencing technologies and more widely available genome sequences, researchers are able to study evolutionary mechanisms of traits via comparative genomic methods. Compared with other vertebrates, bird genomes are relatively small and exhibit conserved synteny with few repetitive elements, which makes them suitable for evolutionary studies. Increasing genomic progress has been reported on the evolution of powered flight, body size variation, beak morphology, plumage colouration, high-elevation colonization, migration, and vocalization. By summarizing previous studies, we demonstrate the genetic bases of trait evolution, highlighting the roles of small-scale sequence variation, genomic structural variation, and changes in gene interaction networks. We suggest that future studies should focus on improving the quality of reference genomes, exploring the evolution of regulatory elements and networks, and combining genomic data with morphological, ecological, behavioural, and developmental biology data. 相似文献
947.
Beiping Zhong Bing Cheng Xiaoming Huang Qian Xiao Zhitong Niu Yu-feng Chen Qiang Yu Wenyu Wang Xiao-Jian Wu 《Cell death & disease》2022,13(1)
Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.Subject terms: Colon cancer, Cancer microenvironment 相似文献
948.
949.
950.
Yu Ruan Jiaqiao Hu Yaping Che Yanyan Liu Zhenhuan Luo Jin Cheng Qi Han He He Qinghua Zhou 《Cell death & disease》2022,13(2)
Mitochondrial dysfunction is becoming one of the main pathology factors involved in the etiology of neurological disorders. Recently, mutations of the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) which encode two homologous proteins that belong to the mitochondrial CHCH domain protein family, are linked to Parkinson’s disease and amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), respectively. However, the physiological and pathological roles of these twin proteins have not been well elaborated. Here, we show that, in physiological conditions, CHCHD2 and CHCHD10 interact with OMA1 and suppress its enzyme activity, which not only restrains the initiation of the mitochondrial integrated response stress (mtISR), but also suppresses the processing of OPA1 for mitochondrial fusion. Further, during mitochondria stress-induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment, CHCHD2 and CHCHD10 translocate to the cytosol and interacte with eIF2a, which attenuates mtISR overactivation by suppressing eIF2a phosphorylation and its downstream response. As such, knockdown of CHCHD2 and CHCHD10 triggers mitochondrial ISR, and such cellular response is enhanced by CCCP treatment. Therefore, our findings demonstrate the first “mtISR suppressor” localized in mitochondria for regulating stress responses in mammalian cells, which has a profound pathological impact on the CHCH2/CHCH10-linked neurodegenerative disorder.Subject terms: Stress signalling, Mitochondria 相似文献