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71.
Scanlan BJ Tuft B Elfrey JE Smith A Zhao A Morimoto M Chmielinska JJ Tejero-Taldo MI Mak IuT Weglicki WB Shea-Donohue T 《Molecular and cellular biochemistry》2007,306(1-2):59-69
The aim of this study was to determine the effect of magnesium deficiency on small intestinal morphology and function. Rats
were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 weeks. Infiltration of neutrophils
and mucosal injury were assessed in stained sections of small intestine. Magnesium deficiency alone induced a significant
increase in neutrophil infiltration and increased vascular ICAM-1 expression, in the absence of changes in mucosal injury
or expression of proinflammatory mediators. Magnesium deficiency was associated with hyposecretory epithelial cell responses
and vascular macromolecular leak in the small intestine and lung, which was attributed partly to reduced expression of NOS-3.
To determine the effect of hypomagnesmia on the intestinal responses to a known oxidative stress, groups of rats were randomized
to either sham operation or superior mesenteric artery occlusion for 10 (non-injurious) or 30 (injurious) minutes followed
by a 1- or 4-hour reperfusion period. In response to mesenteric ischemia/reperfusion, deficient rats showed exaggerated PMN
influx, but similar mucosal injury. Intestinal ischemia in sufficient animals induced vascular macromolecular leak in the
small intestine and lung at 4 hours of reperfusion, with levels similar to those observed in untreated deficient rats. Acute
magnesium repletion of deficient rats 24 h before surgery attenuated the exaggerated inflammation in deficient rats. These
data show that magnesium deficiency induced a subclinical inflammation in the small intestine in the absence of mucosal injury,
but with significant functional changes in local and remote organs and increased sensitivity to oxidative stress.
The opinions contained herein are those of the authors and are not to be construed as official policy or reflecting the views
of the Department of Defense 相似文献
72.
73.
Characterization of Environmental Sources of the Human and Animal Pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States
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Sarah E. Kidd Yat Chow Sunny Mak Paxton J. Bach Huiming Chen Adrian O. Hingston James W. Kronstad Karen H. Bartlett 《Applied microbiology》2007,73(5):1433-1443
Cryptococcus gattii has recently emerged as a primary pathogen of humans and wild and domesticated animals in British Columbia, particularly on Vancouver Island. C. gattii infections are typically infections of the pulmonary and/or the central nervous system, and the incidence of infection in British Columbia is currently the highest reported globally. Prior to this emergence, the environmental distribution of and the extent of colonization by C. gattii in British Columbia were unknown. We characterized the environmental sources and potential determinants of colonization in British Columbia. C. gattii was isolated from tree surfaces, soil, air, freshwater, and seawater, and no seasonal prevalence was observed. The C. gattii concentrations in air samples were significantly higher during the warm, dry summer months, although potentially infectious propagules (<3.3 μm in diameter) were present throughout the year. Positive samples were obtained from many different areas of British Columbia, and some locations were colonization “hot spots.” C. gattii was generally isolated from acidic soil, and geographic differences in soil pH may influence the extent of colonization. C. gattii soil colonization also was associated with low moisture and low organic carbon contents. Most of the C. gattii isolates recovered belonged to the VGIIa genetic subtype; however, sympatric colonization by the VGIIb strain was observed at most locations. At one sampling site, VGIIa, VGIIb, VGI, and the Cryptococcus neoformans serotype AD hybrid all were coisolated. Our findings indicate extensive colonization by C. gattii within British Columbia and highlight an expansion of the ecological niche of this pathogen. 相似文献
74.
75.
Susceptibility to tuberculosis (TB) may be affected by host genetic factors. Elevated levels of transforming growth factor-beta 1 (TGF-β1) were found in plasma of patients with active TB compared with those of healthy contacts. To investigate the association of TGF-β1 gene polymorphisms (C-509T and T869C) and plasma levels with the risk of TB in Hong Kong Chinese adults, a case-control study was carried out on 174 active TB patients and 174 healthy controls matched for age, gender and smoking. Blood samples from 180 blood donors served as another control group. Genotyping was carried out on genomic DNA using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma TGF-β1 was measured by commercially available ELISA kit. We found no differences in the distribution of genotypes or alleles of TGF-β1 gene polymorphisms at C-509T and T869C between patients and either group of healthy controls. Patients with TB had elevated plasma TGF-β1 levels compared with healthy controls irrespective of their genotypes (p < 0.001). In conclusion, TGF-β1 gene polymorphism at C-509T and T869C is not associated with TB susceptibility in Hong Kong Chinese adults, but elevated plasma TGF-β1 levels suggests that this cytokine may play a role in the pathogenesis of tuberculosis. 相似文献
76.
Perez GI Acton BM Jurisicova A Perkins GA White A Brown J Trbovich AM Kim MR Fissore R Xu J Ahmady A D'Estaing SG Li H Kagawa W Kurumizaka H Yokoyama S Okada H Mak TW Ellisman MH Casper RF Tilly JL 《Cell death and differentiation》2007,14(3):524-533
Although the identification of specific genes that regulate apoptosis has been a topic of intense study, little is known of the role that background genetic variance plays in modulating cell death. Using germ cells from inbred mouse strains, we found that apoptosis in mature (metaphase II) oocytes is affected by genetic background through at least two different mechanisms. The first, manifested in AKR/J mice, results in genomic instability. This is reflected by numerous DNA double-strand breaks in freshly isolated oocytes, causing a high apoptosis susceptibility and impaired embryonic development following fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis and improves embryonic development. The second, manifested in FVB mice, results in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with cytochrome c release and a high apoptosis susceptibility, the latter of which is suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of 'normal' mitochondria. Therefore, background genetic variance can profoundly affect apoptosis in female germ cells by disrupting both genomic DNA and mitochondrial integrity. 相似文献
77.
Commerford SR Vargas L Dorfman SE Mitro N Rocheford EC Mak PA Li X Kennedy P Mullarkey TL Saez E 《Molecular endocrinology (Baltimore, Md.)》2007,21(12):3002-3012
The liver X receptors (LXRalpha and beta) are nuclear receptors that coordinate carbohydrate and lipid metabolism. Treatment of insulin-resistant mice with synthetic LXR ligands enhances glucose tolerance, inducing changes in gene expression expected to decrease hepatic gluconeogenesis (via indirect suppression of gluconeogenic enzymes) and increase peripheral glucose disposal (via direct up-regulation of glut4 in fat). To evaluate the relative contribution of each of these effects on whole-body insulin sensitivity, we performed hyperinsulinemic-euglycemic clamps in high-fat-fed insulin-resistant rats treated with an LXR agonist or a peroxisome proliferator-activated receptor gamma ligand. Both groups showed significant improvement in insulin action. Interestingly, rats treated with LXR ligand had lower body weight and smaller fat cells than controls. Insulin-stimulated suppression of the rate of glucose appearance (Ra) was pronounced in LXR-treated rats, but treatment failed to enhance peripheral glucose uptake (R'g), despite increased expression of glut4 in epididymal fat. To ascertain whether LXR ligands suppress hepatic gluconeogenesis directly, mice lacking LXRalpha (the primary isotype in liver) were treated with LXR ligand, and gluconeogenic gene expression was assessed. LXR activation decreased expression of gluconeogenic genes in wild-type and LXRbeta null mice, but failed to do so in animals lacking LXRalpha. Our observations indicate that despite inducing suggestive gene expression changes in adipose tissue in this model of diet-induced insulin resistance, the antidiabetic effect of LXR ligands is primarily due to effects in the liver that appear to require LXRalpha. These findings have important implications for clinical development of LXR agonists as insulin sensitizers. 相似文献
78.
Edgcomb VP Molyneaux SJ Böer S Wirsen CO Saito M Atkins MS Lloyd K Teske A 《Extremophiles : life under extreme conditions》2007,11(2):329-342
Growth and survival of hyperthermophilic archaea in their extreme hydrothermal vent and subsurface environments are controlled
by chemical and physical key parameters. This study examined the effects of elevated sulfide concentrations, temperature,
and acidic pH on growth and survival of two hydrothermal vent archaea (Pyrococcus strain GB-D and Thermococcus fumicolans) under high temperature and pressure regimes. These two strains are members of the Thermococcales, a family of hyperthermophilic,
heterotrophic, sulfur-reducing archaea that occur in high densities at vent sites. As actively growing cells, these two strains
tolerated regimes of pH, pressure, and temperature that were in most cases not tolerated under severe substrate limitation.
A moderate pH of 5.5–7 extends their survival and growth range over a wider range of sulfide concentrations, temperature and
pressure, relative to lower pH conditions. T. fumicolans and Pyrococcus strain GB-D grew under very high pressures that exceeded in-situ pressures typical of hydrothermal vent depths, and included
deep subsurface pressures. However, under the same conditions, but in the absence of carbon substrates and electron acceptors,
survival was generally lower, and decreased rapidly when low pH stress was combined with high pressure and high temperature.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
79.
Nishio M Watanabe K Sasaki J Taya C Takasuga S Iizuka R Balla T Yamazaki M Watanabe H Itoh R Kuroda S Horie Y Förster I Mak TW Yonekawa H Penninger JM Kanaho Y Suzuki A Sasaki T 《Nature cell biology》2007,9(1):36-44
Proper neutrophil migration into inflammatory sites ensures host defense without tissue damage. Phosphoinositide 3-kinase (PI(3)K) and its lipid product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) regulate cell migration, but the role of PtdIns(3,4,5)P(3)-degrading enzymes in this process is poorly understood. Here, we show that Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1), a PtdIns(3,4,5)P(3) phosphatase, is a key regulator of neutrophil migration. Genetic inactivation of SHIP1 led to severe defects in neutrophil polarization and motility. In contrast, loss of the PtdIns(3,4,5)P(3) phosphatase PTEN had no impact on neutrophil chemotaxis. To study PtdIns(3,4,5)P(3) metabolism in living primary cells, we generated a novel transgenic mouse (AktPH-GFP Tg) expressing a bioprobe for PtdIns(3,4,5)P(3.) Time-lapse footage showed rapid, localized binding of AktPH-GFP to the leading edge membrane of chemotaxing ship1(+/+)AktPH-GFP Tg neutrophils, but only diffuse localization in ship1(-/-)AktPH-GFP Tg neutrophils. By directing where PtdIns(3,4,5)P(3) accumulates, SHIP1 governs the formation of the leading edge and polarization required for chemotaxis. 相似文献
80.
Chun C. Mak 《Molecular simulation》2015,41(1-3):156-167
Charge-transfer-to-solvent excited iodide–polar solvent molecule clusters, [I? (Solv)n]*, have attracted substantial interest over the past 20 years as they can undergo intriguing relaxation processes leading ultimately to the formation of gas-phase molecular analogues of the solvated electron. In this review article, we present a comprehensive overview of the development and application of state-of-the-art first-principles molecular dynamics simulation approaches to understand and interpret the results of femtosecond photoelectron spectroscopy experiments on [I? (Solv)n]* relaxation, which point to a high degree of solvent specificity in the electron solvation dynamics. The intricate molecular details of the [I? (Solv)n]* relaxation process are presented, and by contrasting the relaxation mechanisms of clusters with several different solvents (water, methanol and acetonitrile), the molecular basis of the solvent specificity of electron solvation in [I? (Solv)n]* is uncovered, leading to a more refined view of the manifestation of electron solvation in small gas-phase clusters. 相似文献