全文获取类型
收费全文 | 1150篇 |
免费 | 137篇 |
出版年
2023年 | 6篇 |
2022年 | 18篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 17篇 |
2018年 | 32篇 |
2017年 | 25篇 |
2016年 | 44篇 |
2015年 | 69篇 |
2014年 | 50篇 |
2013年 | 70篇 |
2012年 | 111篇 |
2011年 | 107篇 |
2010年 | 75篇 |
2009年 | 41篇 |
2008年 | 76篇 |
2007年 | 64篇 |
2006年 | 63篇 |
2005年 | 44篇 |
2004年 | 46篇 |
2003年 | 52篇 |
2002年 | 38篇 |
2001年 | 23篇 |
2000年 | 13篇 |
1999年 | 13篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1970年 | 4篇 |
1967年 | 2篇 |
排序方式: 共有1287条查询结果,搜索用时 15 毫秒
921.
Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSV type 2 glycoprotein subunit vaccine. 总被引:4,自引:4,他引:0 下载免费PDF全文
Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine. 相似文献
922.
Luca Santini Joseph A. Tobias Corey Callaghan Juan Gallego-Zamorano Ana Benítez-López 《Global Ecology and Biogeography》2023,32(7):1189-1204
Aim
How population density varies across animal species in the context of environmental gradients, and associated migratory strategies, remains poorly understood. The recent influx of avian trait data and population density estimates allows these patterns to be described and explored in unprecedented detail. This study aims to identify the main macroecological drivers of population density in birds.Location
Global.Time period
1970–2021.Major taxa studied
Birds (Aves).Methods
We collated a dataset of 5072 local population density estimates for 1853 species and modelled population density as a function of trait and environmental predictors in a Bayesian framework accounting for phylogenetic and spatial autocorrelation. We explored the influence of body mass, diet, primary lifestyle, mating system, nesting behaviour, territoriality, and migratory behaviour on population density, accounting for a range of environmental variables, including preferred habitat type, primary productivity, precipitation and temperature. Based on this empirical baseline, we then predicted the mean population density for 9089 species of birds and estimated global geographic patterns of bird population density.Results
Population density was lower in species with larger body mass and higher trophic levels, and also declined in territorial species, migratory species, brood parasites and species inhabiting resource-poor habitat types (e.g., deserts). Conversely, population density increased in cooperative breeders. Environmental drivers were most influential for migratory birds, with precipitation and temperature both associated with higher population density. Overall, bird population densities were higher at lower latitudes.Main conclusions
Our results support previous findings on the role of body mass, diet and environmental gradients, but also reveal novel species-specific drivers of avian densities related to reproduction, migration and resource-holding behaviour. Substantial fine-scale variation remains unexplained. We provide a global dataset of population density predictions for use in macroecological analyses and conservation assessments. 相似文献923.
This report describes a lysozyme expressed at high levels in the stomach of
the hoatzin, the only known foregut-fermenting bird. Evolutionary
comparison places it among the calcium-binding lysozymes rather than among
the conventional types. Conventional lysozymes were recruited as digestive
enzymes twice in the evolution of mammalian foregut fermenters, and these
independently recruited lysozymes share convergent structural changes
attributed to selective pressures in the stomach. Biochemical convergence
and parallel amino acid replacements are observed in the hoatzin stomach
lysozyme even though it has a different genetic origin from the mammalian
examples and has undergone more than 300 million years of independent
evolution.
相似文献
924.
Astringency of aqueous solutions of phenolic compounds (grape seed tannins,
tannic acid, catechin and gallic acid) increased upon addition of citric
acid, whereas the astringency of alum was reduced. Astringency of alum was
decreased equivalently by addition of equi-sour levels of lactic acid,
citric acid or hydrochloric acid. The difference between alum and the
phenolic compounds is speculated to result from chemical modifications
affecting binding of the astringents with oral proteins rather than
cognitive differences. Chelation of the aluminum ion in alum by acids
reduces its availability for interacting with salivary proteins or
epithelial proteins. In contrast, the increased astringency produced upon
acidification of phenolic compounds is speculated to result from the pH
driven increase in the affinity of the phenols for binding with proteins.
These results suggest that alum cannot be used interchangeably with
phenolic astringents in psychophysical studies.
相似文献
925.
An important aspect of environmental control in a life-support system is the monitoring and regulation of atmospheric gases (Sager et al. 1988) at concentrations required for the maintenance of all life forms. It will be necessary to know the rates of CO2 use, oxygen evolution, and water flux through evapotranspiration by a crop stand under various environmental conditions, so that appropriate designs and control systems for maintaining mass balances of those gases can be achieved for a full range of environmental regimes. Mass budgets of gases will also enable evaluation of crop health by monitoring directly the rates of gas exchange and indirectly the rate of accumulation of dry matter, based on rates of carbon dioxide use. This article focuses on the unique capabilities of the NASA biomass production chamber for monitoring and evaluating gas exchange rates, with special emphasis on results with wheat and soybean, two candidate species identified by NASA for CELSS. 相似文献
926.
927.
Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals. 相似文献
928.
Cystic fibrosis patients bearing both the common missense mutation, Gly→Asp at codon 551 and the ΔF508 mutation are clinically indistinguishable from ΔF508 homozygotes, except for decreased risk of meconium ileus 下载免费PDF全文
A Hamosh T M King B J Rosenstein M Corey H Levison P Durie L C Tsui I McIntosh M Keston D J Brock 《American journal of human genetics》1992,51(2):245-250
The glycine-to-aspartic acid missense mutation at codon 551 (G551D), which is within the first nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR), is the third most common cystic fibrosis (CF) mutation, with a worldwide frequency of 3.1% among CF chromosomes. Regions with a high frequency correspond to areas with large populations of Celtic descent. To determine whether G551D confers a different phenotype than does delta F508, the most common CF mutation, we studied 79 compound heterozygotes for G551D/delta F508, from nine centers in Europe and North America. Each subject was matched, by age and sex, with a delta F508 homozygote from the same center. A retrospective cohort analysis was performed on the following outcome parameters: age at diagnosis, sweat chloride, meconium ileus at birth, height, weight, weight for height, FVC, FEV1, chest X-ray score, pseudomonas colonization, pancreatic sufficiency, and Shwachman clinical score. There was less meconium ileus among the G551D/delta F508 compound heterozygotes (relative risk 0.33; 95% confidence interval .13-.86), as well as a trend toward later age at diagnosis of pancreatic insufficiency. No statistically significant difference was found between the groups for any other parameter. These results suggest that the CF genotype can be a predictor of pancreatic and intestinal phenotype. Prenatal counseling for the two genotype groups should differ only with respect to probability of meconium ileus. Clinical outcome (after survival of meconium ileus) for G551D/delta F508 compound heterozygotes and delta F508 homozygotes is indistinguishable; therefore, prognostic counseling should not differ. 相似文献
929.
Receptor-mediated action of hepoxilin A3 releases diacylglycerol and arachidonic acid from human neutrophils 总被引:2,自引:0,他引:2
S Nigam S Nodes G Cichon E J Corey C R Pace-Asciak 《Biochemical and biophysical research communications》1990,171(3):944-948
We have previously shown that hepoxilin A3 increases the intracellular concentration of Ca+2 in human neutrophils. Herein we address the initial events of hepoxilin action on the neutrophil which precede the rise in intracellular calcium. We show that hepoxilin A3 at 10-1000 nM concentrations releases from [1-14C]-arachidonic acid labeled neutrophils diacylglycerol and unesterified arachidonic acid in a time and concentration dependent fashion. The release of arachidonic acid and diacyglycerol are receptor-mediated events which are blocked by pertussis toxin. This data shows that hepoxilin A3 stimulates phospholipases C and A2 in the cell which may be involved in the rise in cytosolic calcium. Thus, hepoxilins may represent a hitherto unrecognised class of cellular mediators. 相似文献
930.
Darren W. Engers Sean R. Bollinger Julie L. Engers Joseph D. Panarese Megan M. Breiner Alison Gregro Anna L. Blobaum Joanne J. Bronson Yong-Jin Wu John E. Macor Alice L. Rodriguez Rocio Zamorano P. Jeffrey Conn Craig W. Lindsley Colleen M. Niswender Corey R. Hopkins 《Bioorganic & medicinal chemistry letters》2018,28(15):2641-2646
Previous reports from our laboratory disclosed the structure and activity of a novel 1H-pyrazolo[4,3-b]pyridine-3-amine scaffold (VU8506) which showed excellent potency, selectivity and in vivo efficacy in preclinical rodent models of Parkinson’s disease. Unfortunately, this compound suffered from significant CYP1A2 induction as measured through upstream AhR activation (125-fold) and thus was precluded from further advancement in chronic studies. Herein, we report a new scaffold developed recently which was systematically studied in order to mitigate the CYP1A2 liabilities presented in the earlier scaffolds. We have identified a novel structure that maintains the potency and selectivity of other mGlu4 PAMs, leading to 9i (hmGlu4 EC50?=?43?nM; AhR activation?=?2.3-fold). 相似文献