全文获取类型
收费全文 | 979篇 |
免费 | 9篇 |
国内免费 | 52篇 |
专业分类
1040篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 13篇 |
2018年 | 24篇 |
2017年 | 5篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 60篇 |
2013年 | 59篇 |
2012年 | 48篇 |
2011年 | 119篇 |
2010年 | 99篇 |
2009年 | 88篇 |
2008年 | 134篇 |
2007年 | 112篇 |
2006年 | 78篇 |
2005年 | 79篇 |
2004年 | 18篇 |
2003年 | 20篇 |
2002年 | 17篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 10篇 |
1998年 | 2篇 |
1997年 | 7篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有1040条查询结果,搜索用时 15 毫秒
991.
Juyeon Lee Boyeon Park Gayoung Kim Kwangwoo Kim Jeongjun Pak Kwanhyeong Kim Michael B. Ye Sung-Gyoo Park Daeho Park 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014
Elmo is an evolutionarily conserved mammalian ortholog of Caenorhabditis elegans CED-12 with proposed roles during the removal of apoptotic cells, cell migration, neurite outgrowth, and myoblast fusion (Katoh and Negishi (2003) [1], Park and Tosello (2007) [2], Grimsley et al. (2004) [3], Hamoud et al. (2014) [4]). Elmo mediates these cellular processes by interacting with various proteins located in the plasma membrane, cytoplasm and nucleus, and by modulating their activities although it has no intrinsic catalytic activity (Park and Tosello (2007) [2], Hamoud et al. (2014) [4], Li et al. (2013) [5], Margaron, Fradet and Cote (2013) [6], and Mauldin et al. (2013)[7]). Because there are a limited number of proteins known to interact with Elmo, we performed a yeast two-hybrid screen using Elmo1 as bait to identify Elmo1-interacting proteins and to evaluate their mode of regulation. Arhgef16 was one of the proteins identified through the screen and subsequent analyses revealed that Arhgef16 interacted with Elmo1 in mammalian cells as well. Expression of Arhgef16 in phagocytes promoted engulfment of apoptotic cells, and engulfment mediated by Arhgef16 increased synergistically in the presence of Elmo1 but was abrogated in the absence of Elmo1. In addition, Arhgef16-mediated removal of apoptotic cells was dependent on RhoG, but independent of Dock1. Taken together, this study suggests that the newly identified Elmo1-interacting protein, Arhgef16, functions synergistically with Elmo1 to promote clearance of apoptotic cells in a RhoG-dependent and Dock1-independent manner. 相似文献
992.
993.
Diego Moreira de Souza Átila Clivea Martins Luciano Jensen Wilson Wasielesky Jr José María Monserrat 《Marine and Freshwater Behaviour and Physiology》2014,47(1):1-10
A 10-day trial was conducted to evaluate the effect of temperature on the antioxidant system of Litopenaeus vannamei in a biofloc technology system. Four treatments in triplicate tanks were assigned to the following temperatures: 15, 21, 27 (control), and 33 °C and the water quality parameters were monitored every day. For all enzyme assays, the hemolymph cells lysate of six shrimp per treatment was collected. Lipid peroxidation (LPO) was assessed by determining the content of thiobarbituric acid-reactive substances (TBARS); the activities of catalase (CAT) and glutathione-S-transferase (GST) were also evaluated. The results of TBARS showed that shrimp reared at 15 and 21 °C presented an increase of 407% (240 h) and 339% (120 h), respectively. L. vannamei exposed to 15 °C augmented in 186% (24 h) the activity of CAT. Moreover, shrimp of 21 °C group also increased CAT activity in 228% (6 h). GST presented the strongest variation reaching 1437% in shrimp of 15 °C for 6 h and 1425% of the 21 °C treatment at the same time. All these results were compared to the initial time (27 °C). Moreover, the antioxidant system was not sufficient to counteract LPO; therefore, the animals reared in 15 and 21 °C presented higher enzyme activities, suggesting that cold water can induce the oxidative stress in L. vannamei. 相似文献
994.
《Gene expression patterns : GEP》2016,20(1-2):120-128
Patched-related (Ptr) encodes a protein with 12 potential transmembrane domains and a sterol-sensing domain that is closely related in predicted topology and domain organization to Patched, the canonical receptor of the Hedgehog pathway. Here we describe the production of an antibody specific for Drosophila Ptr and analyse its spatial and temporal distribution in the embryo. We find that at early developmental stages Ptr is predominantly localized at cell periphery but later on it becomes strongly and almost exclusively expressed in hemocytes. Interestingly Ptr null mutant embryos died without hatching. Our findings suggest that Ptr plays an essential function in Drosophila development, perhaps as a new receptor of embryonic hemocytes. 相似文献
995.
Ina Kycia Srikanth Kudithipudi Raluca Tamas Goran Kungulovski Arunkumar Dhayalan Albert Jeltsch 《Journal of molecular biology》2014
PHF1 associates with the Polycomb repressive complex 2 and it was demonstrated to stimulate its H3K27-trimethylation activity. We studied the interaction of the PHF1 Tudor domain with modified histone peptides and found that it recognizes H3K36me3 and H3tK27me3 (on the histone variant H3t) and that it uses the same trimethyllysine binding pocket for the interaction with both peptides. Since both peptide sequences are very different, this result indicates that reading domains can have dual specificities. Sub-nuclear localization studies of full-length PHF1 in human HEK293 cells revealed that it co-localizes with K27me3, but not with K36me3, and that this co-localization depends on the trimethyllysine binding pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain. Our data suggest that PHF1 binds to H3tK27me3 in human chromatin, and H3t has a more general role in Polycomb regulation. 相似文献
996.
997.
Increasing attention is being paid to the possibility of applying chemopreventive agents for the protection of individuals from cancer risk. The beneficial potential of chemoprotective compounds is usually well documented by extensive experimental data. To assure the desired effect, these compounds are frequently concentrated to produce dietary supplements for human use. The additive and synergistic effects of other food constituents are, however, frequently ignored. Even natural chemopreventive compounds have to be considered as xenobiotics. Thus, as much attention has to be paid to their testing prior to their wide application as is usual in drug development for human treatment. Unfortunately, much of the research in this area is solely based on simplified in vitro systems that cannot take into account the complexity of biotransformation processes, e.g. chemopreventive compound-drug interaction, effect on metabolism of endogenic compounds. Hence, the predicted chemopreventive potential is not attained in respect of cancer prevention; moreover, the administration of high doses of chemopreventive compounds might be even detrimental for the human health. 相似文献
998.
Ma?gorzata Ga?a?yn-Sidorczuk Ma?gorzata M. Brzóska Maria Jurczuk Janina Moniuszko-Jakoniuk 《Chemico-biological interactions》2009,180(1):31-203
The study was aimed to estimate whether rat's exposure to cadmium (Cd; 50 mg/l in drinking water for 12 weeks) and/or ethanol (EtOH; 5 g/kg b.wt./24 h p.o. for 12 weeks), noted by us to induce oxidative stress and stimulate lipid peroxidation, can cause oxidative damage to proteins and DNA, and whether and to what extent the effects of co-exposure differ from those observed under the treatment with each substance alone. Protein carbonyl groups (PC) and protein thiol groups (PSH) in the serum, liver and kidney, as markers of oxidative protein damage, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the serum, as a marker of DNA oxidation, were determined. The exposure to Cd or/and EtOH led to oxidative protein damage (increased PC and decreased PSH concentrations in the serum and/or liver), and to DNA oxidation (increased 8-OHdG concentration in the serum). The effects were more advanced at the co-exposure than at the treatment with each substance alone. The more serious damage to proteins and DNA at the co-exposure to Cd and EtOH seems to be the effect of independent action of both xenobiotics. The results of the present paper together with our recent findings in the same rats seem to indicate that at co-exposure to Cd and EtOH proteins and DNA may be more vulnerable to oxidation than lipids. The paper is the first report suggesting that excessive EtOH consumption during exposure to Cd may increase the risk of health damage via enhancing protein and DNA oxidation. 相似文献
999.
D. Truong 《Chemico-biological interactions》2009,180(1):79-88
Diallyl disulfide (DADS) and diallyl sulfide (DAS) are the major metabolites found in garlic oil and have been reported to lower cholesterol and prevent cancer. The molecular cytotoxic mechanisms of DADS and DAS have not been determined.The cytotoxic effectiveness of hydrogen versus allyl sulfides towards hepatocytes was found to be as follows: NaHS > DADS > DAS. Hepatocyte mitochondrial membrane potential was decreased and reactive oxygen species (ROS) and TBARS formation was increased by all three allyl sulfides. (1) DADS induced cytotoxicity was prevented by the H2S scavenger hydroxocobalamin, which also prevented cytochrome oxidase dependent mitochondrial respiration suggesting that H2S inhibition of cytochrome oxidase contributed to DADS hepatocyte cytotoxicity. (2) DAS cytotoxicity on the other hand was prevented by hydralazine, an acrolein trap. Hydralazine also prevented DAS induced GSH depletion, decreased mitochondrial membrane potential and increased ROS and TBARS formation. Chloral hydrate, the aldehyde dehydrogenase 2 inhibitor, however had the opposite effects, which could suggest that acrolein contributed to DAS hepatocyte cytotoxicity. 相似文献
1000.
Calmodulin-regulated protein phosphorylation plays a pivotal role in amplifying and diversifying the action of calcium ion. In this study, we identified a calmodulin-binding receptor-like protein kinase (CBRLK1) that was classified into an S-locus RLK family. The plasma membrane localization was determined by the localization of CBRLK1 tagged with a green fluorescence protein. Calmodulin bound specifically to a Ca2+-dependent calmodulin binding domain in the C-terminus of CBRLK1. The bacterially expressed CBRLK1 kinase domain could autophosphorylate and phosphorylates general kinase substrates, such as myelin basic proteins. The autophosphorylation sites of CBRLK1 were identified by mass spectrometric analysis of phosphopeptides.