全文获取类型
收费全文 | 202篇 |
免费 | 20篇 |
出版年
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 10篇 |
2013年 | 14篇 |
2012年 | 13篇 |
2011年 | 9篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 10篇 |
2005年 | 8篇 |
2004年 | 3篇 |
2003年 | 8篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1996年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1948年 | 1篇 |
1936年 | 1篇 |
1902年 | 1篇 |
1901年 | 1篇 |
1900年 | 1篇 |
1892年 | 1篇 |
排序方式: 共有222条查询结果,搜索用时 46 毫秒
121.
Joshua Pajak Erik Dill Emilio Reyes-Aldrete Mark A White Brian A Kelch Paul
J Jardine Gaurav Arya Marc
C Morais 《Nucleic acids research》2021,49(11):6474
Double-stranded DNA viruses package their genomes into pre-assembled capsids using virally-encoded ASCE ATPase ring motors. We present the first atomic-resolution crystal structure of a multimeric ring form of a viral dsDNA packaging motor, the ATPase of the asccφ28 phage, and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Based on these results, and previous single-molecule data and cryo-EM reconstruction of the homologous φ29 motor, we propose an overall packaging model that is driven by helical-to-planar transitions of the ring motor. These transitions are coordinated by inter-subunit interactions that regulate catalytic and force-generating events. Stepwise ATP binding to individual subunits increase their affinity for the helical DNA phosphate backbone, resulting in distortion away from the planar ring towards a helical configuration, inducing mechanical strain. Subsequent sequential hydrolysis events alleviate the accumulated mechanical strain, allowing a stepwise return of the motor to the planar conformation, translocating DNA in the process. This type of helical-to-planar mechanism could serve as a general framework for ring ATPases. 相似文献
122.
123.
124.
sirt1-null mice develop an autoimmune-like condition 总被引:1,自引:0,他引:1
Sequeira J Boily G Bazinet S Saliba S He X Jardine K Kennedy C Staines W Rousseaux C Mueller R McBurney MW 《Experimental cell research》2008,314(16):3069-3074
The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease. 相似文献
125.
Lipid corrections in carbon and nitrogen stable isotope analyses: comparison of chemical extraction and modelling methods 总被引:4,自引:0,他引:4
Logan JM Jardine TD Miller TJ Bunn SE Cunjak RA Lutcavage ME 《The Journal of animal ecology》2008,77(4):838-846
1. Lipids have more negative delta(13)C values relative to other major biochemical compounds in plant and animal tissues. Although variable lipid content in biological tissues alters results and conclusions of delta(13)C analyses in aquatic food web and migration studies, no standard correction protocol exists. 2. We compared chemical extraction and mathematical correction methods for freshwater and marine fishes and aquatic invertebrates to better understand impacts of correction approaches on carbon (delta(13)C) and nitrogen (delta(15)N) stable isotope data. 3. Fish and aquatic invertebrate tissue delta(13)C values increased significantly following extraction for almost all species and tissue types relative to nonextracted samples. In contrast, delta(15)N was affected for muscle and whole body samples from only a few freshwater and marine species and had a limited effect for the entire data set. 4. Lipid normalization models, using C : N as a proxy for lipid content, predicted lipid-corrected delta(13)C for paired data sets more closely with parameters specific to the tissue type and species to which they were applied. 5. We present species- and tissue-specific models based on bulk C : N as a reliable alternative to chemical extraction corrections. By analysing a subset of samples before and after lipid extraction, models can be applied to the species and tissues of interest that will improve estimates of dietary sources using stable isotopes. 相似文献
126.
N R Hartman L A Trimble J C Vederas I Jardine 《Biochemical and biophysical research communications》1985,133(3):964-971
The primary biliary metabolite of cyclosporine has been isolated from rabbit and human bile. The material has been identified by mass spectrometry and by nuclear magnetic resonance spectrometry as an acidic metabolite of cyclosporine in which the eta-methyl group of the cyclosporine-specific nine carbon amino acid #1 has been oxidized to an alpha, beta unsaturated carboxylic acid functionality. This major cyclosporine metabolite is inactive in a phytohemagglutinin stimulated lymphocyte proliferation assay. 相似文献
127.
Carlene A. Hamilton Catherine A. Howie Emma Jardine John L. Reid 《Free radical research》1998,28(3):251-257
The effects of the xanthine oxidase/hypoxanthine free radical generating system on endothelium dependent and independent relaxation were compared in aortic rings from New Zealand white rabbits and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits with mild atherosclerosis. Studies were carried out in young (3 months) and mature (18 months) animals. Plasma cholesterol levels were significantly higher in both 3 and 18 month WHHL animals. Endothelium independent relaxation to SNP did not differ between groups. However, the attenuation of relaxation to carbachol after xanthine oxidase/hypoxanthine treatment tended to be less in WHHL. This reached significance at 18 but not 3 months. We propose that this could be due to increases in levels of endogenous scavenger enzymes in these WHHL rabbits. 相似文献
128.
129.
Céline Aguer Melissa Pasqua A. Brianne Thrush Cynthia Moffat Michael McBurney Karen Jardine Rui Zhang Brittany Beauchamp Robert Dent Ruth McPherson Mary-Ellen Harper 《生物化学与生物物理学报:疾病的分子基础》2013,1832(10):1624-1633
Muscle insulin resistance is linked to oxidative stress and decreased mitochondrial function. However, the exact cause of muscle insulin resistance is still unknown. Since offspring of patients with type 2 diabetes mellitus (T2DM) are susceptible to developing insulin resistance, they are ideal for studying the early development of insulin resistance. By using primary muscle cells derived from obese non-diabetic subjects with (FH +) or without (FH ?) a family history of T2DM, we aimed to better understand the link between mitochondrial function, oxidative stress, and muscle insulin resistance. Insulin-stimulated glucose uptake and glycogen synthesis were normal in FH + myotubes. Resting oxygen consumption rate was not different between groups. However, proton leak was higher in FH + myotubes. This was associated with lower ATP content and decreased mitochondrial membrane potential in FH + myotubes. Surprisingly, mtDNA content was higher in FH + myotubes. Oxidative stress level was not different between FH + and FH ? groups. Reactive oxygen species content was lower in FH + myotubes when differentiated in high glucose/insulin (25 mM/150 pM), which could be due to higher oxidative stress defenses (SOD2 expression and uncoupled respiration). The increased antioxidant defenses and mtDNA content in FH + myotubes suggest the existence of compensatory mechanisms, which may provisionally prevent the development of insulin resistance. 相似文献
130.
Katherine V. Clark-Knowles Danielle Dewar-Darch Karen E. Jardine Michael W. McBurney 《PloS one》2013,8(11)
The protein deacetylase SIRT1 has been implicated in the regulation of a large number of cellular processes that are thought to be required for cancer initiation and progression. There are conflicting data that make it unclear whether Sirt1 functions as an oncogene or tumor suppressor. To assess the effect of SIRT1 on the emergence and progression of mammary tumors, we crossed mice that harbor a point mutation that abolishes SIRT1 catalytic activity with mice carrying the polyoma middle T transgene driven by the murine mammary tumor virus promoter (MMTV-PyMT). The absence of SIRT1 catalytic activity neither accelerated nor blocked the formation of tumors and metastases in this model. There was a lag in tumor latency that modestly extended survival in Sirt1 mutant mice that we attribute to a delay in mammary gland development and not to a direct effect of SIRT1 on carcinogenesis. These results are consistent with previous evidence suggesting that Sirt1 is not a tumor promoter or a tumor suppressor. 相似文献