全文获取类型
收费全文 | 327篇 |
免费 | 41篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 12篇 |
2015年 | 13篇 |
2014年 | 12篇 |
2013年 | 9篇 |
2012年 | 18篇 |
2011年 | 16篇 |
2010年 | 14篇 |
2009年 | 11篇 |
2008年 | 21篇 |
2007年 | 12篇 |
2006年 | 11篇 |
2005年 | 17篇 |
2004年 | 13篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 15篇 |
2000年 | 8篇 |
1999年 | 11篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 7篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 5篇 |
1932年 | 1篇 |
1924年 | 1篇 |
排序方式: 共有368条查询结果,搜索用时 218 毫秒
81.
The HIV Env-mediated fusion reaction 总被引:22,自引:0,他引:22
Gallo SA Finnegan CM Viard M Raviv Y Dimitrov A Rawat SS Puri A Durell S Blumenthal R 《Biochimica et biophysica acta》2003,1614(1):36-50
The current general model of HIV viral entry involves the binding of the trimeric viral envelope glycoprotein gp120/gp41 to cell surface receptor CD4 and chemokine co-receptor CXCR4 or CCR5, which triggers conformational changes in the envelope proteins. Gp120 then dissociates from gp41, allowing for the fusion peptide to be inserted into the target membrane and the pre-hairpin configuration of the ectodomain to form. The C-terminal heptad repeat region and the leucine/isoleucine zipper region then form the thermostable six-helix coiled-coil, which drives the membrane merger and eventual fusion. This model needs updating, as there has been a wealth of data produced in the last few years concerning HIV entry, including target cell dependencies, fusion kinetic data, and conformational intermediates. A more complete model must include the involvement of membrane microdomains, actin polymerization, glycosphingolipids, and possibly CD4 and chemokine signaling in entry. In addition, kinetic experiments involving the addition of fusion inhibitors have revealed some of the rate-limiting steps in this process, adding a temporal component to the model. A review of these data that may require an updated version of the original model is presented here. 相似文献
82.
Zhang J Bárdos T Shao Q Tschopp J Mikecz K Glant TT Finnegan A 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(7):3495-3503
Activation-induced cell death (AICD) of T cells is one of the major mechanisms of peripheral tolerance. The regulation of AICD by IL-4 is poorly understood. In this study, we report that AICD in IL-4-deficient T cells is significantly reduced compared with that in wild-type T cells. This impaired AICD correlates with the failure to induce degradation of cellular FLIP. IL-4-mediated enhancement of AICD and cellular FLIP degradation requires a Janus kinase/STAT-6 signaling pathway. Unexpectedly, these effects of IL-4 could be blocked by a neutralizing anti-IL-2 Ab, and addition of rIL-2 could completely restore the defective AICD in IL-4-deficient T cells. Furthermore, IL-4 regulates the T cell thresholds for IL-2 signaling during AICD. These data suggest that IL-4 promotes AICD via an IL-2-dependent mechanism. 相似文献
83.
Polygalacturonase inhibiting protein (PGIP) is localized in plant cell walls and plays an important role both in pectic substance metabolism and in prevention of the penetration of phytopathogenic microorganisms. Apparently, PGIP is responsible for the specificity of cell--cell interactions during pollination or inoculation by fungi nonpathogenic for the particular plant. PGIPs from different plants share a basic common structure. They are rather thermostable glycoproteins enriched with leucine and contain about 20% carbohydrates; the molecular weight varies between 37-54 kD. The synthesis of PGIP is encoded by one gene, and its expression is stimulated by injury and fungal infection. The resistance of plant tissues to infection frequently correlates with PGIP expression and with inhibiting action on fungal PG. Thus, PGIP is believed to be useful for gene engineering to obtain transgenic plants resistant to fungal infection or retaining commercial value during storage. 相似文献
84.
Jeffrey A. Jankowski Jennifer M. Finnegan R. Mark Wightman 《Journal of neurochemistry》1994,63(5):1739-1747
Abstract: The temporal resolution of carbon-fiber microelectrodes has been exploited to examine the plasticity of quantal secretory events at individual adrenal medullary cells. The size of individual quantal events, monitored by amperometric oxidation of released catecholamines, was found to be dependent on the extracellular ionic composition, the secretagogue, and the order of depolarization delivery. Release was observed with either exposure to 60 m M K+ in the presence of Ca2+ or exposure to 3 m M Ba2+ in solutions of different pH, with and without external Ca2+ . Ba2+ was demonstrated to induce Ca2+ -independent exocytotic release for an extended period of time (>4 min) relative to release induced by K+ (∼30 s), which is Ca2+ dependent. In all cases, simultaneous changes of intracellular divalent cations, monitored by fura-2 fluorescence, accompanied quantal release and had a similar time course. Exocytosis caused by Ba2+ in Ca2+ -free medium had a larger mean spike area at pH 8.2 than at pH 7.4. When Ba2+ -induced spikes measured at pH 7.4 were compared, the spikes in Ca2+ -free medium were found to be broader and shorter but had the same area. Release induced by K+ after exposure to Ba2+ was comprised of larger quantal events when compared with preceding K+ stimulations. Finally, spikes obtained with Ba2+ exposure at an extracellular pH of 5.5 had a different shape than those obtained in more basic solutions. These changes in spike size and shape are consistent with the interactions between catecholamines and other intravesicular components. 相似文献
85.
Purification and characterization of Klebsiella aerogenes UreE protein: a nickel-binding protein that functions in urease metallocenter assembly. 总被引:22,自引:0,他引:22 下载免费PDF全文
M. H. Lee H. S. Pankratz S. Wang R. A. Scott M. G. Finnegan M. K. Johnson J. A. Ippolito D. W. Christianson R. P. Hausinger 《Protein science : a publication of the Protein Society》1993,2(6):1042-1052
The Klebsiella aerogenes ureE gene product was previously shown to facilitate assembly of the urease metallocenter (Lee, M.H., et al., 1992, J. Bacteriol. 174, 4324-4330). UreE protein has now been purified and characterized. Although it behaves as a soluble protein, UreE is predicted to possess an amphipathic beta-strand and exhibits unusually tight binding to phenyl-Sepharose resin. Immunogold electron microscopic studies confirm that UreE is a cytoplasmic protein. Each dimeric UreE molecule (M(r) = 35,000) binds 6.05 + 0.25 nickel ions (Kd of 9.6 +/- 1.3 microM) with high specificity according to equilibrium dialysis measurements. The nickel site in UreE was probed by X-ray absorption and variable-temperature magnetic circular dichroism spectroscopies. The data are most consistent with the presence of Ni(II) in pseudo-octahedral geometry with 3-5 histidyl imidazole ligands. The remaining ligands are nitrogen or oxygen donors. UreE apoprotein has been crystallized and analyzed by X-ray diffraction methods. Addition of nickel ion to apoprotein crystals leads to the development of fractures, consistent with a conformational change upon binding nickel ion. We hypothesize that UreE binds intracellular nickel ion and functions as a nickel donor during metallocenter assembly into the urease apoprotein. 相似文献
86.
Jansen Smith Marina C. Rillo Ádám T. Kocsis Maria Dornelas David Fastovich Huai-Hsuan M. Huang Lukas Jonkers Wolfgang Kiessling Qijian Li Lee Hsiang Liow Miranda Margulis-Ohnuma Stephen Meyers Lin Na Amelia M. Penny Kate Pippenger Johan Renaudie Erin E. Saupe Manuel J. Steinbauer Mauro Sugawara Adam Tomašovỳch John W. Williams Moriaki Yasuhara Seth Finnegan Pincelli M. Hull 《Global Ecology and Biogeography》2023,32(10):1680-1689
Motivation
We have little understanding of how communities respond to varying magnitudes and rates of environmental perturbations across temporal scales. BioDeepTime harmonizes assemblage time series of presence and abundance data to help facilitate investigations of community dynamics across timescales and the response of communities to natural and anthropogenic stressors. BioDeepTime includes time series of terrestrial and aquatic assemblages of varying spatial and temporal grain and extent from the present-day to millions of years ago.Main Types of Variables Included
BioDeepTime currently contains 7,437,847 taxon records from 10,062 assemblage time series, each with a minimum of 10 time steps. Age constraints, sampling method, environment and taxonomic scope are provided for each time series.Spatial Location and Grain
The database includes 8752 unique sampling locations from freshwater, marine and terrestrial ecosystems. Spatial grain represented by individual samples varies from quadrats on the order of several cm2 to grid cells of ~100 km2.Time Period and Grain
BioDeepTime in aggregate currently spans the last 451 million years, with the 10,062 modern and fossil assemblage time series ranging in extent from years to millions of years. The median extent of modern time series is 18.7 years and for fossil series is 54,872 years. Temporal grain, the time encompassed by individual samples, ranges from days to tens of thousands of years.Major Taxa and Level of Measurement
The database contains information on 28,777 unique taxa with 4,769,789 records at the species level and another 271,218 records known to the genus level, including time series of benthic and planktonic foraminifera, coccolithophores, diatoms, ostracods, plants (pollen), radiolarians and other invertebrates and vertebrates. There are to date 7012 modern and 3050 fossil time series in BioDeepTime.Software Format
SQLite, Comma-separated values. 相似文献87.
88.
First-egg date fluctuations for the Pied Flycatcher Ficedula hypoleuca in the woodlands of mid-Wales in the twentieth century 总被引:1,自引:1,他引:0
EM. SLATER 《Ibis》1999,141(3):497-499
89.
90.
Waterhouse J Nevill A Finnegan J Williams P Edwards B Kao SY Reilly T 《Chronobiology international》2005,22(1):121-136
The disruption of circadian rhythms following time-zone transitions gives rise to the syndrome of jet lag. The power of some of the symptoms of jet lag to predict the amount of jet lag measured at the same and at different times of the day has been investigated. Eleven healthy subjects were studied in an Isolation Unit for two days after a simulated flight from the UK to Beijing (8 time zones to the east). At six time-points (08:30, 11:00, 14:00, 17:00, 20:00, and 23:00 h), the subjects recorded their jet lag, and the differences from "normal" (that is, from days in which there is no jet lag) of alertness, hunger, indigestion, concentration, motivation, and irritability. They recorded at 08:30 h the type of food they had eaten since rising at 08:00h and, at the other times, the type of food eaten in the last three hours. Assessments were made by visual analogue scales or, in the case of type of food, by a nominal scale. Following the time-zone transition, the adjustment of meals appeared to be complete almost immediately. Jet lag and its symptoms were present during both experimental days. Jet lag tended to rise during the course of the daytime, accompanied by falls in alertness, motivation, and concentration. Correlation matrices between jet lag and each of the other variables were produced, using lags between the variable (from up to 5 time-points before the assessment of jet lag to 5 time-points afterwards) and pooling the results from both days. These matrices indicated that significant correlations existed only between jet lag and alertness, concentration, and motivation, and then only when these other variables were assessed at the same time as jet lag or 1 or 2 time-points earlier. Jet lag was then treated as the dependent variable and the symptoms as covariates in analysis of covariances (ANCOVAs), with the days treated as a random effect. This analysis enabled the significance of potential predictors of jet lag, together with their beta-coefficients (the relationship between a unit change of each significant predictor and the change in jet lag), to be calculated. Falls in alertness and motivation were significant predictors of increased jet lag, provided that they were measured at the same time, when they accounted for about 50% of the jet lag; when measured at other time-points, they did not act as significant predictors. It is concluded that the amount of jet lag varies during the course of the day and that it can be predicted from contemporaneous assessments of alertness and motivation-but not from assessments made at other times of the day, nor from other variables that are symptoms of jet lag, even though these other variables are significantly increased. In considering the results of this and our previous study, we reiterate the view that the exact meaning of "jet lag" is complex and that the particular combination of factors that contribute to it might vary with the time of day that the assessment is made. Inferences about any decrements due to time-zone transitions cannot be made reliably at times of the day that differ from the time when jet lag is assessed. 相似文献