全文获取类型
收费全文 | 433篇 |
免费 | 43篇 |
出版年
2023年 | 4篇 |
2021年 | 14篇 |
2020年 | 6篇 |
2019年 | 8篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 16篇 |
2015年 | 27篇 |
2014年 | 38篇 |
2013年 | 14篇 |
2012年 | 40篇 |
2011年 | 33篇 |
2010年 | 27篇 |
2009年 | 24篇 |
2008年 | 20篇 |
2007年 | 34篇 |
2006年 | 32篇 |
2005年 | 24篇 |
2004年 | 20篇 |
2003年 | 31篇 |
2002年 | 22篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1984年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有476条查询结果,搜索用时 31 毫秒
1.
2.
3.
Karine Salin Sonya K. Auer Agata M. Rudolf Graeme J. Anderson Andrew G. Cairns William Mullen Richard C. Hartley Colin Selman Neil B. Metcalfe 《Biology letters》2015,11(9)
There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2
in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. 相似文献
4.
5.
6.
7.
Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii 下载免费PDF全文
Wei Qiu Amy Wernimont Keliang Tang Sonya Taylor Vladimir Lunin Matthieu Schapira Sarah Fentress Raymond Hui L David Sibley 《The EMBO journal》2009,28(7):969-979
Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X‐ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate‐binding site. ROP kinases contain a typical bilobate kinase fold and a novel N‐terminal extension that both stabilizes the N‐lobe and provides a unique means of regulation. Although ROP2 and ROP8 were catalytically inactive, they provided a template for homology modelling of the active kinase ROP18, a major virulence determinant of T. gondii. Autophosphorylation of key residues in the N‐terminal extension resulted in ROP18 activation, which in turn phosphorylated ROP2 and ROP8. Mutagenesis and mass spectrometry experiments revealed that ROP18 was maximally activated when this phosphorylated N‐terminus relieved autoinhibition resulting from extension of aliphatic side chains into the ATP‐binding pocket. This novel means of regulation governs ROP kinases implicated in parasite virulence. 相似文献
8.
Marie‐Josée Demers Sonya Thibodeau Dominique Noël Naoya Fujita Takashi Tsuruo Rémy Gauthier Mélina Arguin Pierre H. Vachon 《Journal of cellular biochemistry》2009,107(4):639-654
Herein, we investigated the survival roles of Fak, Src, MEK/Erk, and PI3‐K/Akt‐1 in intestinal epithelial cancer cells (HCT116, HT29, and T84), in comparison to undifferentiated and differentiated intestinal epithelial cells (IECs). We report that: (1) cancer cells display striking anoikis resistance, as opposed to undifferentiated/differentiated IECs; (2) under anoikis conditions and consequent Fak down‐activation, cancer cells nevertheless exhibit sustained Fak–Src interactions and Src/MEK/Erk activation, unlike undifferentiated/differentiated IECs; however, HCT116 and HT29 cells exhibit a PI3‐K/Akt‐1 down‐activation, as undifferentiated/differentiated IECs, whereas T84 cells do not; (3) cancer cells require MEK/Erk for survival, as differentiated (but not undifferentiated) IECs; however, T84 cells do not require Fak and HCT116 cells do not require PI3‐K/Akt‐1, in contrast to the other cells studied; (4) Src acts as a cornerstone in Fak‐mediated signaling to MEK/Erk and PI3‐K/Akt‐1 in T84 cells, as in undifferentiated IECs, whereas PI3‐K/Akt‐1 is Src‐independent in HCT116, HT29 cells, as in differentiated IECs; and (5) EGFR activity inhibition abrogates anoikis resistance in cancer cells through a loss of Fak–Src interactions and down‐activation of Src/MEK/Erk (T84, HCT116, HT29 cells) and PI3‐K/Akt‐1 (T84 cells). Hence, despite distinctions in signaling behavior not necessarily related to undifferentiated or differentiated IECs, intestinal epithelial cancer cells commonly display an EGFR‐mediated sustained activation of Src under anoikis conditions. Furthermore, such sustained Src activation confers anoikis resistance at least in part through a consequent sustenance of Fak–Src interactions and MEK/Erk activation, thus not only overriding Fak‐mediated signaling to MEK/Erk and/or PI3‐K/Akt‐1, but also the requirement of Fak and/or PI3‐K/Akt‐1 for survival. J. Cell. Biochem. 107: 639–654, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
9.
Huizhi Zhao Dong Wang Bing Liu Xingpeng Jiang Jing Zhang Ming Fan Zhengjie Fan Ying Chen Sonya Wei Song Wei Gao Tianzi Jiang Qinghua Cui 《Biochemical and biophysical research communications》2009,379(3):702-705
The fact that microRNAs play a role in almost all biological processes is well established, as is the importance of recombination in generating genome variability. However, the association between microRNAs and recombination remains largely unknown. In order to investigate the recombination patterns of microRNAs, we performed a comprehensive analysis of the recombination rate of human microRNAs. We observed that microRNAs that are expressed in several tissues tend to have lower recombination rates than tissue-specific microRNAs. Additionally, microRNAs that are associated with a number of diseases are also likely to have lower recombination rates. Furthermore, microRNAs with higher expression levels are found to have fewer recombination events. These findings reveal patterns in recombination rates of microRNAs that could help in understanding the function, evolution, and disease-related roles of microRNAs. 相似文献
10.