首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   119篇
  免费   3篇
  2021年   3篇
  2020年   3篇
  2019年   2篇
  2018年   2篇
  2017年   1篇
  2016年   2篇
  2015年   5篇
  2014年   4篇
  2013年   5篇
  2012年   7篇
  2011年   7篇
  2010年   4篇
  2009年   12篇
  2008年   6篇
  2007年   6篇
  2006年   12篇
  2005年   4篇
  2004年   2篇
  2003年   5篇
  2002年   5篇
  2000年   1篇
  1999年   1篇
  1998年   2篇
  1997年   3篇
  1996年   4篇
  1995年   1篇
  1994年   1篇
  1991年   1篇
  1988年   1篇
  1985年   1篇
  1984年   2篇
  1983年   1篇
  1981年   3篇
  1979年   1篇
  1975年   2篇
排序方式: 共有122条查询结果,搜索用时 31 毫秒
71.
In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP-sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-) currents in alveolar monolayers. In addition, it was shown previously that a K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism possibly related to epithelial sodium channels (ENaC). We therefore hypothesized that prolonged treatment with K(+) channel modulators could induce a sustained regulation of ENaC activity and/or expression. Alveolar monolayers were treated for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR. Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal transepithelial current, amiloride-sensitive Na(+) current, and forskolin-activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them. Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha-ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment. Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar fluid transport was found to be driven, at least in part, by Na(+) transport through ENaC, we tested the impact of K(+) channel modulators on fluid absorption across alveolar monolayers. We found that glibenclamide and clofilium reduced fluid absorption to a level similar to that seen in the presence of amiloride, whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance.  相似文献   
72.
73.

Background

Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age among Canadians aged 25–85, stratified by sex and use of antiresorptive agents.

Methods

We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995–1997, and at 3-year (participants aged 40–60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change.

Results

Bone loss in all 3 skeletal sites began among women at age 40–44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50–54 who were transitioning from premenopause to postmenopause, with a change from baseline of –6.8% (95% confidence interval [CI] –7.5% to –4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25–39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50–79.

Interpretation

The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.Low bone mineral density is one of the most important risk factors for fracture.1,2,3–7 Treatment with antiresorptive agents has been widely used for several decades, and the results of randomized controlled trials have shown that at least part of their efficacy is associated with their capacity to increase or stabilize bone density.4 Although clinical guidelines recommend measurement of bone density, among other important risk factors, when assessing a patient''s risk for fracture,3,8,9 there is no international consensus on the optimal age at which to begin measurement, or on the frequency of measurement.10 The Canadian guidelines recommend it for patients aged 65 and older, even in the absence of risk factors or treatment, and suggest a frequency of every 2–3 years.8 Furthermore, it has been suggested that the rate of decline rather than a single measurement of bone density may better identify patients with an elevated risk for fracture.11 Consequently, determining changes in bone density over time may provide clues on the pathophysiology of fractures and provide more accurate estimates of the optimal timing for repeat measurement.Previous studies of change in bone mineral density as a function of age have had a number of limitations. Many were cross-sectional; had small samples, limited age ranges or differing inclusion and exclusion criteria; and most excluded men.12–20 The third National Health and Nutrition Examination Survey,21 a large cross-sectional study based in the United States included women and men aged 20 years and older but excluded only those who were pregnant or who had a fracture in both hips. It reported that, based on a single measurement of bone density in the hip, age-dependent bone loss in the hips begins early (20–40 years) and continues in both sexes throughout life. Cross-sectional data from the ongoing Canadian Multicentre Osteoporosis Study suggested that, although this finding may hold true for the femoral neck, which consists of both cortical and trabecular bone, it is not true for the largely trabecular lumbar spine.22 Furthermore, the use of cross-sectional data to estimate changes over time has fundamental limitations: the effect of age cannot be separated from the effect of birth cohort and survivorship, and estimates are based on between-group differences rather than changes in an individual participant.The use of longitudinal data would allow examination of the rate of change of bone mineral density over time with and without antiresorptive therapy. We sought to assess the average rate of change in bone density as a function of age among Canadians aged 25–85, stratified by sex and use of antiresorptive agents.  相似文献   
74.
Three prenylated flavonoids 5,7,4'-trihydroxy-3'(3-methylbut-2-enyl)-3-methoxy flavone, 5,7-dihydroxy-3'(3-methylbut-2-enyl)-3,4'-dimethoxy flavone and 5,7,4'-trihydroxy-3',5'(3-methylbuyt-2-enyl)-3-methoxy flavone together with three other known flavonoids were isolated from the medicinal plant Dodonaea polyandra. The plant is used in the traditional medicine system of Northern Kaanju people of Cape York Peninsula, Queensland, Australia. The extracts studied have previously been found to possess anti-inflammatory activity. Successive fractionation of leaf and stem extracts by column and high performance liquid chromatography led to the isolation of these compounds. Their structures were determined using a number of spectroscopic techniques including 1D and 2D NMR and high resolution mass spectroscopy. The structural elucidation is reported herein accompanied by full 1H and 13C NMR spectroscopic data. Spectroscopic data of known compounds was in agreement with that previously reported in literature.  相似文献   
75.
In genetically diverse insect societies (polygynous or polyandrous queens), the production of new queens can set the ground for competition among lineages. This competition can be very intense when workers can reproduce using thelytoky as worker lineages that manage to produce new queens gain a huge benefit. Selection at the individual level might then lead to the evolution of cheating genotypes, i.e. genotypes that reproduce more than their fair share. We studied the variation in reproductive success among worker patrilines in the thelytokous and highly polyandrous ant Cataglyphis cursor. Workers produce new queens by thelytoky in orphaned colonies. The reproductive success of each patriline was assessed in 13 orphaned colonies using genetic analysis of 433 workers and 326 worker-produced queens. Our results show that patrilines contributed unequally to queen production in half of the colonies, and the success of patrilines was function of their frequencies in workers. However, over all colonies, we observed a significant difference in the distribution of patrilines between workers and worker-produced queens, and this difference was significant in three of 13 colonies. In addition, six colonies contained a low percentage of foreign workers (drifters), and in one colony, they produced a disproportionably high number of queens. Hence, we found some evidence for the occurrence of rare cheating genotypes. Nevertheless, cheating appears to be less pronounced than in the Cape Honey bee, a species with a similar reproductive system. We argue that worker reproduction by parthenogenesis might not be common in natural populations of C. cursor.  相似文献   
76.
77.

Background

Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.

Methods and Findings

We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2×10−19). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI −0.01, 0.01]; p = 1.00; n = 46,186); fasting insulin (0.01 pmol/l [95% CI −0.00, 0.01,]; p = 0.22; n = 46,186); BMI (0.00 kg/m2 [95% CI −0.01, 0.01]; p = 0.80; n = 127,587); bone mineral density (0.01 g/cm2 [95% CI −0.01, 0.03]; p = 0.36; n = 32,961); mean arterial pressure (−0.06 mm Hg [95% CI −0.19, 0.07]); p = 0.36; n = 28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p = 0.76; n = 9,580/53,810).

Conclusions

DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP. Please see later in the article for the Editors'' Summary  相似文献   
78.
Tremendous efforts have been invested in the development of the internet of things during the past 10 years. Implantable sensors still need embedded miniaturized energy harvesting devices, since commercialized thin films and microbatteries do not provide sufficient power densities and suffer from limited lifetime. Therefore, micro‐supercapacitors are good candidates to store energy and deliver power pulses while providing non‐constant voltage output with time. However, multistep expensive protocols involving mask aligners and sophisticated cleanrooms are used to prepare these devices. Here, a simple and versatile laser‐writing procedure to integrate flexible micro‐supercapacitors and microbatteries on current‐collector‐free polyimide foils is reported, starting from commercial powders. Ruthenium oxide (RuO2)‐based micro‐supercapacitors are prepared by laser irradiation of a bilayered tetrachloroauric acid (HAuCl4 · 3H2O)–cellulose acetate/RuO2 film deposited by spin‐coating, which leads to adherent Au/RuO2 electrodes with a unique pillar morphology. The as‐prepared microdevices deliver 27 mF cm?2/540 F cm?3 in 1 m H2SO4 and retain 80% of the initial capacitance after 10 000 cycles. This simple process is applied to make carbon‐based micro‐supercapacitors, as well as metal oxide based pseudocapacitors and battery electrodes, thus offering a straightforward solution to prepare low‐cost flexible microdevices at a large scale.  相似文献   
79.
ABSTRACT Guadeloupe Woodpeckers (Melanerpes herminieri) are the only endemic bird species on the Caribbean island of Guadeloupe. These woodpeckers were classified as Near Threatened on the IUCN Red List following a population survey in 1994. To reassess the Guadeloupe Woodpecker population, we conducted a new survey in 2007, with 21 transects distributed across eight habitats known to be used by the woodpeckers. Habitats with the highest estimated population densities were seasonal evergreen secondary growth forest, followed by swamp forest and rainforest. Surveys revealed an estimated population of 8469 pairs in 2007 compared to 7368 pairs in 1994, a difference that was not significant. However, our 2007 survey revealed that Guadeloupe Woodpeckers had recolonized the last large patch of available forest on Basse‐Terre, one of the two main islands in the Guadeloupe archipelago. Although our results suggest that the Guadeloupe Woodpecker population has remained relatively stable since 1994, deforestation remains a serious threat and we recommend that the IUCN Red List status of Near Threatened be retained. Management measures that would benefit Guadeloupe Woodpeckers include halting deforestation and providing financial support to people on private land to plant trees and leave dead trees standing. Regular monitoring will be important for determining the possible effects of such measures on the Guadeloupe Woodpecker population.  相似文献   
80.
The impact of feed supplementation with bambermycin, monensin, narasin, virginiamycin, chlortetracycline, penicillin, salinomycin, and bacitracin on the distribution of Escherichia coli pathotypes in broiler chickens was investigated using an E. coli virulence DNA microarray. Among 256 E. coli isolates examined, 59 (23%) were classified as potentially extraintestinal pathogenic E. coli (ExPEC), while 197 (77%) were considered commensal. Except for chlortetracycline treatment, the pathotype distribution was not significantly different among treatments (P > 0.05). Within the 59 ExPEC isolates, 44 (75%) were determined to be potentially avian pathogenic E. coli (APEC), with the remaining 15 (25%) considered potentially “other” ExPEC isolates. The distribution within phylogenetic groups showed that 52 (88%) of the ExPEC isolates belonged to groups B2 and D, with the majority of APEC isolates classified as group D and most commensal isolates (170, 86%) as group A or B1. Indirect assessment of the presence of the virulence plasmid pAPEC-O2-ColV showed a strong association of the plasmid with APEC isolates. Among the 256 isolates, 224 (88%) possessed at least one antimicrobial resistance gene, with nearly half (107, 42%) showing multiple resistance genes. The majority of resistance genes were distributed among commensal isolates. Considering that the simultaneous detection of antimicrobial resistance tet(A), sulI, and blaTEM genes and the integron class I indicated a potential presence of the resistance pAPEC-O2-R plasmid, the results revealed that 35 (14%) of the isolates, all commensals, possessed this multigene resistance plasmid. The virulence plasmid was never found in combination with the antimicrobial resistance plasmid. The presence of the ColV plasmid or the combination of iss and tsh genes in the majority of APEC isolates supports the notion that when found together, the plasmid, iss, and tsh serve as good markers for APEC. These data indicate that different resistant E. coli pathotypes can be found in broiler chickens and that the distribution of such pathotypes and certain virulence determinants could be modulated by antimicrobial agent feed supplementation.Several classes of antimicrobial agents, such as glycolipids (bambermycin), cyclic peptides (bacitracin), ionophores (monensin and salinomycin), streptogramins (virginiamycin), and β-lactams (penicillin), are widely used as food additives in modern animal husbandry to prevent infections and promote growth (6). Increasing antimicrobial resistance in animals and its potential threat to human health led to the ban of bacitracin, spiramycin, tylosin, and virginiamycin as feeding additives by the European Union in 1999 (7, 46). Although this precautionary measure is still controversial because of being seen as having a negligible impact on human health, negative consequences for animal health and welfare, including economic losses for farmers, were subsequently observed in Europe (7). In stark contrast, however, the ban has been beneficial in reducing the total quantity of antibiotics administered to food animals (7, 47). Under good production conditions and correct use of antibiotics, poultry production is reported to be competitive (14, 47, 48) and even beneficial in reducing antimicrobial resistance in important food animal reservoirs and thus the potential threat to public health (48).Escherichia coli is generally considered a commensal member of the normal gastrointestinal microflora in humans and animals, yet some strains are known to cause serious morbidity and mortality. The expression of various virulence factors, which affect cellular processes, can result in different clinical diseases, such as cystitis, pyelonephritis, sepsis/meningitis, and gastroenteritis. The possession of different virulence gene subsets can further define the E. coli pathotype (31). The extraintestinal pathogenic E. coli (ExPEC) strains are epidemiologically and phylogenetically distinct from both intestinal pathogenic and commensal strains (43). In North America, annually, several million cases of urinary tract infections, abdominal infections, pelvic infections, pneumonia, meningitis, and sepsis are caused by ExPEC (42). In poultry production, avian pathogenic E. coli (APEC) is responsible for significant economic losses. APEC strains induce extraintestinal diseases such as air sacculitis, colibacillosis, polysorositis, and septicemia in birds (9, 21, 22, 31, 35, 45). Although no specific set of virulence factors has been clearly linked to APEC strains, most identified virulence factors are similar to those frequently associated with ExPEC (36).Bearing in mind that the avian intestinal environment has been considered a reservoir of E. coli having zoonotic potential (15) and the possible contamination of poultry products with such bacteria during slaughter, the impact of antimicrobial feeding additives on the distribution and dissemination of bacterial pathotypes and antibiotic resistance needs to be explored to address human, animal, and environmental health concerns. To this end, an E. coli DNA virulence microarray previously employed to assess the genotypes (virulence and antibiotic resistance genes) of E. coli strains isolated from different environmental ecosystems and from the chicken intestinal tract (1, 10, 19, 20, 33) was used. The aim of the present trial was to investigate the distributions of pathotypes and of virulence and antibiotic resistance genes in E. coli isolates from broilers fed with antimicrobial supplementation diets including bambermycin, penicillin, salinomycin, bacitracin, chlortetracycline, virginiamycin, monensin, and narasin.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号