全文获取类型
收费全文 | 1707篇 |
免费 | 149篇 |
国内免费 | 6篇 |
出版年
2023年 | 7篇 |
2022年 | 16篇 |
2021年 | 36篇 |
2020年 | 15篇 |
2019年 | 15篇 |
2018年 | 41篇 |
2017年 | 21篇 |
2016年 | 38篇 |
2015年 | 84篇 |
2014年 | 81篇 |
2013年 | 111篇 |
2012年 | 120篇 |
2011年 | 114篇 |
2010年 | 75篇 |
2009年 | 85篇 |
2008年 | 109篇 |
2007年 | 86篇 |
2006年 | 83篇 |
2005年 | 86篇 |
2004年 | 88篇 |
2003年 | 89篇 |
2002年 | 75篇 |
2001年 | 11篇 |
1999年 | 13篇 |
1998年 | 25篇 |
1997年 | 15篇 |
1996年 | 7篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1988年 | 10篇 |
1985年 | 10篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 15篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 10篇 |
1976年 | 10篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1971年 | 10篇 |
1968年 | 11篇 |
1963年 | 7篇 |
1962年 | 8篇 |
1960年 | 6篇 |
排序方式: 共有1862条查询结果,搜索用时 15 毫秒
131.
Sheila L. Flack Louise M. BallLeena A. Nylander-French 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(27):2635-2642
1,6-Hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenges in HDI biomarker analysis including the quantification of N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N′-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA) in urine samples based on previously established methods for HDA analysis. In addition, we describe the optimization of reaction conditions for the synthesis of monoacetyl-HDA and diacetyl-HDA, and utilize these standards for the quantification of these metabolites in the urine of three occupationally exposed workers. Diacetyl-HDA was present in untreated urine at 0.015–0.060 μg/l. Using base hydrolysis, the concentration range of monoacetyl-HDA in urine was 0.19–2.2 μg/l, 60-fold higher than in the untreated samples on average. HDA was detected only in one sample after base hydrolysis (0.026 μg/l). In contrast, acid hydrolysis yielded HDA concentrations ranging from 0.36 to 10.1 μg/l in these three samples. These findings demonstrate HDI metabolism via N-acetylation metabolic pathway and protein adduct formation resulting from occupational exposure to HDI. 相似文献
132.
Liene Dhooghe Sheila Maregesi Daneel Ferreira Filip Lemière Paul Cos Arnold Vlietinck Luc Pieters 《Phytochemistry》2010,71(7):785-791
Preliminary screening of a series of medicinal plants, traditionally used in Tanzania, showed an IC50 of 15.6-31.2 μg/ml for the crude extract of the root of Ormocarpum kirkii S. Moore (Papilionaceae) against Plasmodium falciparum. A bioguided isolation was performed in order to isolate the active constituents. Twelve constituents were obtained and identified using NMR and MS data, and optical rotation measurements. The compounds comprised seven (I-3,II-3)-biflavonoids, three (I-3,II-3)-bi-4-phenyldihydrocoumarins, an isoflavanone and a C-glucosylated flavone. Six compounds, liquiritigeninyl-(I-3,II-3)-naringenin, apigeninyl-(I-3,II-3)-naringenin, 7-O-β-D-glucopyranosylchamaejasmin, (3R,4S,3″R,4″S)-5,5″-di-O-methyldiphysin, 7-O-β-D-glucopyranosyldiphysin, and 4″-hydroxydiphysolone, were isolated in addition to six known components. The compounds were evaluated for antimicrobial activity in a broad screening panel, including P. falciparum. Seven of these showed antiplasmodial activity; isochamaejasmin being the most active with an IC50 of 7.3 ± 3.8 μM, but the selectivity was rather limited. Thus, these constituents may contribute, at least in part, to the antimalarial use of O. kirkii in traditional medicine. 相似文献
133.
Hugo Asselin Serge Payette Marie-Josée Fortin Sheila Vallée 《Journal of Biogeography》2003,30(11):1709-1718
Aim Present northern distribution limit of jack pine (Pinus banksiana Lamb.) follows the northern limit of continuous open boreal forest in western Canada, but not in eastern Canada where it is located further south. We tested the hypothesis that fire plays a more important role than climate in explaining the present position of the northern distribution limit of jack pine. Location An experimental jack pine plantation was set up in 1992, c. 300 km north of the present distribution limit of the species, in the Boniface river area of northern Québec (57°43′ N, 76°05′ W). Methods Climate and fire data were used to compare sites at and north of the present distribution limit of jack pine. In 2001, surviving individuals from the plantation were measured (total height, annual shoot elongation, basal diameter, and presence/absence of cones). Results Climate data from the ten weather stations used in this study did not show major differences. The northern limit of jack pine distribution is closely associated with the occurrence of fires larger than 200 ha. Survival of the planted jack pines was 31%. About 25% of the surviving pines qualified as normal, single‐stem individuals; the others were slightly uprooted and/or showed marks of erosion or foraging. Cones were produced, although no viable seeds were found. Main conclusions The low number of degree‐days above 5 °C at the plantation site could explain why the seeds were not viable. However, such climate conditions are not sufficient to prevent growth, as was shown by annual shoot elongation measurements. Most of the surviving jack pines from the Boniface river plantation are relatively healthy and follow a normal developmental programme. Low fire frequency and small fire size are amongst the main factors that prevented P. banksiana from migrating further north or east following deglaciation in northern Québec and Labrador. 相似文献
134.
Stone KL Bjornson RD Blasko GG Bruce C Cofrancesco R Carriero NJ Colangelo CM Crawford JK Crawford JM daSilva NC Deluca JD Elliott JI Elliott MM Flory PJ Folta-Stogniew EJ Gulcicek E Kong Y Lam TT Lee JY Lin A LoPresti MB Mane SM McMurray WJ Tikhonova IR Westman S Williams NA Wu TL Hongyu Z Williams KR 《The Yale journal of biology and medicine》2007,80(4):195-211
135.
136.
Devlin AM Singh R Wade RE Innis SM Bottiglieri T Lentz SR 《The Journal of biological chemistry》2007,282(51):37082-37090
Alterations in lipid metabolism may play a role in the vascular pathology associated with hyperhomocysteinemia (HHcy). Homocysteine is linked to lipid metabolism through the methionine cycle and the synthesis of phosphatidylcholine (PC) by phosphatidylethanolamine (PE) methyltransferase, which is responsible for the synthesis of 20-40% of liver PC. The goal of the present study was to determine if the reduced methylation capacity in HHcy is associated with alterations in liver phospholipid and fatty acid metabolism. Mice heterozygous for disruption of cystathionine beta-synthase (Cbs+/-) fed a diet to induce HHcy (HH diet) had higher (p<0.001) plasma total homocysteine (30.8+/-4.4 microM, mean+/-S.E.) than C57BL/6 mice (Cbs+/+) fed the HH diet (7.0+/-1.1 microM) or Cbs+/+ mice fed a control diet (2.3+/-0.3 microM). Mild and moderate HHcy was accompanied by lower adenosylmethionine/adenosylhomocysteine ratios (p<0.05), higher PE (p<0.05) and PE/PC ratios (p<0.01), lower PE methyltransferase activity (p<0.001), and higher linoleic acid (p<0.05) and lower arachidonic acid (p<0.05) in PE. Mice with moderate HHcy also had higher linoleic acid and alpha-linolenic acid (p<0.05) and lower arachidonic acid and docosahexaenoic acid (p<0.05) in liver PC. The first step in the desaturation and elongation of linoleic acid and linolenic acid to arachidonic acid and docosahexaenoic acid, respectively, is catalyzed by Delta6-desaturase (encoded by Fads2). We found hypermethylation of the Fads2 promoter (p<0.01), lower Fads2 mRNA (p<0.05), and lower Delta6-desaturase activity (p<0.001) in liver from mice with HHcy. These findings suggest that methylation silencing of liver Fads2 expression and changes in liver fatty acids may contribute to the pathology of HHcy. 相似文献
137.
Tse HM Milton MJ Schreiner S Profozich JL Trucco M Piganelli JD 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(2):908-917
Successful Ag activation of naive T helper cells requires at least two signals consisting of TCR and CD28 on the T cell interacting with MHC II and CD80/CD86, respectively, on APCs. Recent evidence demonstrates that a third signal consisting of proinflammatory cytokines and reactive oxygen species (ROS) produced by the innate immune response is important in arming the adaptive immune response. In an effort to curtail the generation of an Ag-specific T cell response, we targeted the synthesis of innate immune response signals to generate Ag-specific hyporesponsiveness. We have reported that modulation of redox balance with a catalytic antioxidant effectively inhibited the generation of third signal components from the innate immune response (TNF-alpha, IL-1beta, ROS). In this study, we demonstrate that innate immune-derived signals are necessary for adaptive immune effector function and disruption of these signals with in vivo CA treatment conferred Ag-specific hyporesponsiveness in BALB/c, NOD, DO11.10, and BDC-2.5 mice after immunization. Modulating redox balance led to decreased Ag-specific T cell proliferation and IFN-gamma synthesis by diminishing ROS production in the APC, which affected TNF-alpha levels produced by CD4(+) T cells and impairing effector function. These results demonstrate that altering redox status can be effective in T cell-mediated diseases such as autoimmune diabetes to generate Ag-specific immunosuppression because it inhibits the third signal necessary for CD4(+) T cells to transition from expansion to effector function. 相似文献
138.
Sheila K. Schueller 《Evolutionary ecology》2007,21(1):81-98
A match between floral and pollinator traits, such as that between unique island plants and pollinators, is often thought
to be the product of pollinator-mediated selection. I examined whether the floral morphology of an introduced hummingbird-pollinated
plant, Nicotiana glauca (tree tobacco, Solanaceae), is under selection by pollinators on the California Channel Islands where it is a recent colonist.
I first determined differences in floral morphology and pollinator composition between island and mainland populations of
N. glauca. I found that island plants have detectably longer corollas (on average 1 mm) and are visited by hummingbird species with
on average 1–2 mm longer bills than common mainland visitors. Corolla length differences were not found to be associated with
site abiotic differences. Flower size does not vary consistently with season and corolla width is very consistent across sites.
I tested whether island–mainland corolla length differences are the product of pollinator-mediated selection by measuring
phenotypic selection and per visit effectiveness. Contrary to expectations, a longer corolla was not consistently associated
with higher pollen transfer or seed count on the islands. Per visit effectiveness of longer and shorter-billed hummingbirds
did differ; however, effectiveness did not depend on corolla length. Although I failed to detect expected patterns of selection
for longer corollas on islands, I cannot rule out weak or past pollinator-mediated selection. It is also possible that despite
the apparent match between pollinator and floral traits, island–mainland differences in corolla length are instead due to
other environmental effects, selection unrelated to pollinators, or stochastic processes such as drift. 相似文献
139.
Sheila Gahagan 《BMJ (Clinical research ed.)》2007,335(7624):782-783
140.
BACKGROUND: Helicobacter pylori infection leads to gastritis, peptic ulcer, and gastric cancer, in part due to epithelial damage following bacteria binding to the epithelium. Infection with cag pathogenicity island (PAI) bearing strains of H. pylori is associated with increased gastric inflammation and a higher incidence of gastroduodenal diseases. It is now known that various effector molecules are injected into host epithelial cells via a type IV secretion apparatus, resulting in cytoskeletal changes and chemokine secretion. Whether binding of bacteria and subsequent apoptosis of gastric epithelial cells are altered by cag PAI status was examined in this study. METHODS: AGS, Kato III, and N87 human gastric epithelial cell lines were incubated with cag PAI-positive or cag PAI-negative strains of H. pylori in the presence or absence of clarithromycin. Binding was evaluated by flow cytometry and scanning electron microscopy. Apoptosis was assessed by detection of DNA degradation and ELISA detection of exposed histone residues. RESULTS: cag PAI-negative strains bound to gastric epithelial cells to the same extent as cag PAI-positive strains. Both cag PAI-positive and cag PAI-negative strains induced apoptosis. However, cag PAI-positive strains induced higher levels of DNA degradation. Incubation with clarithromycin inactivated H. pylori but did not affect binding. However, pretreatment with clarithromycin decreased infection-induced apoptosis. CONCLUSIONS: cag PAI status did not affect binding of bacteria to gastric epithelial cells but cag PAI-positive H. pylori induced apoptosis more rapidly than cag PAI-negative mutant strains, suggesting that H. pylori binding and subsequent apoptosis are differentially regulated with regard to bacterial properties. 相似文献