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   474篇
  免费   62篇
  536篇
  2021年   10篇
  2019年   5篇
  2018年   5篇
  2017年   7篇
  2016年   8篇
  2015年   10篇
  2014年   16篇
  2013年   19篇
  2012年   16篇
  2011年   18篇
  2010年   22篇
  2009年   10篇
  2008年   20篇
  2007年   14篇
  2006年   15篇
  2005年   13篇
  2004年   18篇
  2003年   7篇
  2002年   10篇
  2001年   17篇
  2000年   13篇
  1999年   8篇
  1998年   9篇
  1997年   6篇
  1994年   4篇
  1993年   4篇
  1992年   16篇
  1991年   10篇
  1990年   11篇
  1989年   9篇
  1988年   9篇
  1987年   15篇
  1986年   9篇
  1985年   14篇
  1984年   15篇
  1983年   8篇
  1982年   5篇
  1981年   9篇
  1980年   10篇
  1979年   6篇
  1978年   5篇
  1977年   11篇
  1976年   8篇
  1975年   8篇
  1974年   4篇
  1973年   6篇
  1972年   4篇
  1971年   5篇
  1969年   7篇
  1968年   5篇
排序方式: 共有536条查询结果,搜索用时 13 毫秒
51.
The Na-K pump in cardiac Purkinje strands has been carefully studied with voltage clamp and Na+-selective microelectrodes. In three of these studies both the rate of change of intracellular Na+ activity, a(Nai), after pump blockade, and the time constant of reduction of a(Nai) after an Na+ load were measured. These two parameters can be employed with a formalism relating pump activity to a(Nai) in order to predict the a(Nai) in the steady state. Several formalisms were tested: (a) a first-order dependence on a(Nai); (b) a model based on the assumption of a single, saturable, Na+-binding site that must be occupied for transport to occur; (c) a model based on n equivalent, saturable, Na+ binding sites per pump molecule all of which must be occupied for transport to occur. The first two models predicted an a(Nai) that is far below the value of about 6 mM that is experimentally obtained. The third model would work for n greater than or equal to 4. These results suggest that either the cardiac Na-K pump is not well described by available Na-K pump models for n less than 4 or that the measured Na+ influx rate, extrusion rate or a(Nai) are in error.  相似文献   
52.
The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.  相似文献   
53.
Pulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO2, end-tidal CO2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO2 (98% ± 3% compared with 95% ± 1%), end-tidal CO2 (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE.Abbreviations: LV, left ventricle; PAP, pulmonary arterial pressure; PE, pulmonary embolism; RV, right ventriclePulmonary embolism (PE) is one of the leading causes of noncardiac sudden death in Western nations and is the third most common cause of cardiovascular morbidity.4,6,7,18 In survivors, severe PE damages the right heart, leading to a clinical course complicated by hypotension and circulatory shock, suggesting acute right heart failure in about 10% of patients and followed by persistent pulmonary hypertension or right ventricular dysfunction and dyspnea in at least 15% of patients.9,15,16,23,29 To test treatments to reduce right heart failure, a standardized model that is repeatable, accurate, and precise and that mimics the gross pathologic, cardiovascular, pulmonary, autonomic, hematologic, biochemical, and cellular characteristics of PE in humans with disease is needed.8Three lines of rationale favor domestic pigs as a model for PE. Several publications, using different methods of anesthesia, have found that swine manifest hemodynamic responses similar to those of humans in the presence of autologous PE, including elevated heart rate, decreased cardiac output, and reduced oxygen saturation.2,12,30 Swine have similar platelet concentrations, and their coagulation profile on thromboelastography has been shown to be similar to humans, with the exception of higher fibrin crosslinking but less fibrin, leading to resistance to plasmin.5,11,19,34 Market swine, which would otherwise be destined for slaughter, are relatively cost effective compared with other large animals and are of sufficient size for placement of an adult pulmonary arterial catheter for measurement of pulmonary vascular resistance in a closed-chest preparation.In view of the differences in the hemodynamic effects of different anesthetic agents, the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. However, current literature lacks a methodologic publication that compares the cardiovascular, right ventricular, pulmonary, and hematologic responses to PE in closed-chest swine models incorporating different anesthetic regimens.Figure 1 presents features of an ideal animal model for the purpose of testing treatments for PE. To develop a swine model of PE that closely resembles this physiologic ideal model, we induced PE in swine maintained in a surgical plane of anesthesia with either isoflurane or α-chloralose. Each of these agents has potential advantages and disadvantages. Isoflurane can be titrated minute by minute but causes undesirable vasodilation, whereas α-chloralose is believed to preserve cardiovascular reflexes but requires heating to dissolve and continuous infusion or repeated boluses.26,35 We hypothesized that, compared with isoflurane, α-chloralose would meet more of the features described in Figure 1.Open in a separate windowFigure 1.Desirable features of large animal model of severe submassive PE designed for translational research.  相似文献   
54.
55.
The past twenty years have revealed the existence of numerous ion channel mutations resulting in human pathology. Ion channels provide the basis of diverse cellular functions, ranging from hormone secretion, excitation–contraction coupling, cell signaling, immune response, and trans-epithelial transport. Therefore, the regulation of biophysical properties of channels is vital in human physiology. Only within the last decade has the role of non-ion channel components come to light in regard to ion channel spatial, temporal, and biophysical regulation in physiology. A growing number of auxiliary components have been determined to play elemental roles in excitable cell physiology, with dysfunction resulting in disorders and related manifestations. This review focuses on the broad implications of such dysfunction, focusing on disease-causing mutations that alter interactions between ion channels and auxiliary ion channel components in a diverse set of human excitable cell disease. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé  相似文献   
56.
A sampling study using a BG-Sentinel trap baited with CO(2), a gravid trap baited with an oak-pine infusion, a human subject, and a vegetative aspirator was conducted to compare their reliability at detecting Aedes albopictus Skuse in suburban and sylvatic habitats. We collected 73,849 mosquitoes, representing 29 species from 11 genera over a 20-wk period. The BG-Sentinel trap accounted for over 85% of all Ae. albopictus captured and was significantly more effective at detecting the presence of Ae. albopictus compared with the other three techniques. Landing counts provided the fewest mosquito species (n = 10), yet provided a quick and effective weekly assessment of the major biting species and were the most effective method for sampling Ae. albopictus within a 10-min period. Fewer Ae. albopictus were sampled from sylvatic habitats compared with suburban ones. Sampling criteria advantageous for surveying Ae. albopictus and other mosquito species are discussed.  相似文献   
57.

Background

Culicoides biting midges (Diptera: Ceratopogonidae) are the biological vectors of globally significant arboviruses of livestock including bluetongue virus (BTV), African horse sickness virus (AHSV) and the recently emerging Schmallenberg virus (SBV). From 2006–2009 outbreaks of BTV in northern Europe inflicted major disruption and economic losses to farmers and several attempts were made to implicate Palaearctic Culicoides species as vectors. Results from these studies were difficult to interpret as they used semi-quantitative RT-PCR (sqPCR) assays as the major diagnostic tool, a technique that had not been validated for use in this role. In this study we validate the use of these assays by carrying out time-series detection of BTV RNA in two colony species of Culicoides and compare the results with the more traditional isolation of infectious BTV on cell culture.

Methodology/Principal Findings

A BTV serotype 1 strain mixed with horse blood was fed to several hundred individuals of Culicoides sonorensis (Wirth & Jones) and C. nubeculosus (Mg.) using a membrane-based assay and replete individuals were then incubated at 25°C. At daily intervals 25 Culicoides of each species were removed from incubation, homogenised and BTV quantified in each individual using sqPCR (Cq values) and virus isolation on a KC-C. sonorensis embryonic cell line, followed by antigen enzyme-linked immunosorbent assay (ELISA). In addition, comparisons were also drawn between the results obtained with whole C. sonorensis and with individually dissected individuals to determine the level of BTV dissemination.

Conclusions/Significance

Cq values generated from time-series infection experiments in both C. sonorensis and C. nubeculosus confirmed previous studies that relied upon the isolation and detection of infectious BTV. Implications on the testing of field-collected Culicoides as potential virus vectors by PCR assays and the use of such assays as front-line tools for use in diagnostic laboratories in this role are discussed.  相似文献   
58.
Aerobically grown enrichment cultures derived from hydrocarbon-contaminated seawater and freshwater sediments were generated by growth on crude oil as sole carbon source. Both cultures displayed a high rate of degradation for a wide range of hydrocarbon compounds. The bacterial species composition of these cultures was investigated by PCR of the 16S rDNA gene using multiple primer combinations. Near full-length 16S rDNA clone libraries were generated and screened by restriction analysis prior to sequence analysis. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) was carried out using two other PCR primer sets targeting either the V3 or V6-V8 regions, and sequences derived from prominent DGGE bands were compared to sequences obtained via cloning. All data sets suggested that the seawater culture was dominated by alpha-subgroup proteobacteria, whereas the freshwater culture was dominated by members of the beta- and gamma-proteobacteria. However, the V6-V8 primer pair was deficient in the recovery of Sphingomonas-like 16S rDNA due to a 3' terminal mismatch with the reverse primer. Most 16S rDNA sequences recovered from the marine enrichment were not closely related to genera containing known oil-degrading organisms, although some were detected. All methods suggested that the freshwater enrichment was dominated by genera containing known hydrocarbon-degrading species.  相似文献   
59.
Enterococcus faecalis is a gram-positive bacterium that is part of the indigenous microbiotica of humans and animals as well as an opportunistic pathogen. In this study, we have fractionated the membrane proteome of E. faecalis and identified many of its constituents by mass spectrometry. We present blue native-/SDS-PAGE reference maps that contain 102 proteins. These proteins are important for cellular homeostasis, virulence, and antibiotic intervention. Intriguingly, many proteins with no known function were also identified, indicating that there are substantial gaps in the knowledge of this organism's biology. On a more limited scale, we also provide insight into the composition of membrane protein complexes. This study is a first step toward elucidating the membrane proteome of E. faecalis, which is critical for a better understanding of how this bacterium interacts with a host and with the extracellular milieu.  相似文献   
60.
Synthesis of an arylsulfone hydroxamate lead optimization library is presented. Biological activity of representative examples is given to demonstrate the value of this approach for lead optimization.  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