全文获取类型
收费全文 | 692篇 |
免费 | 51篇 |
国内免费 | 1篇 |
专业分类
744篇 |
出版年
2023年 | 2篇 |
2022年 | 12篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 13篇 |
2016年 | 14篇 |
2015年 | 27篇 |
2014年 | 32篇 |
2013年 | 63篇 |
2012年 | 55篇 |
2011年 | 54篇 |
2010年 | 34篇 |
2009年 | 33篇 |
2008年 | 52篇 |
2007年 | 43篇 |
2006年 | 33篇 |
2005年 | 34篇 |
2004年 | 35篇 |
2003年 | 22篇 |
2002年 | 38篇 |
2001年 | 2篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1975年 | 2篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1962年 | 2篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有744条查询结果,搜索用时 15 毫秒
71.
Ashwin Sankar Kevin Thorpe Daniel I. McIsaac Jin Luo Duminda N. Wijeysundera Andrea S. Gershon 《CMAJ》2023,195(2):E62
Background:Chronic obstructive pulmonary disease (COPD) is common among surgical patients, and patients with COPD have higher risk for complications and death within 30 days after surgery. We sought to describe the longer-term postoperative survival and costs of patients with COPD compared with those without COPD within 1 year after inpatient elective surgery.Methods:In this retrospective population-based cohort study, we used linked health administrative databases to identify all patients undergoing inpatient elective surgery in Ontario, Canada, from 2005 to 2019. We ascertained COPD status using validated definitions. We followed participants for 1 year after surgery to evaluate survival and costs to the health system. We quantified the association of COPD with survival (Cox proportional hazards models) and costs (linear regression model with log-transformed costs) with partial adjustment (for sociodemographic factors and procedure type) and full adjustment (also adjusting for comorbidities). We assessed for effect modification by frailty, cancer and procedure type.Results:We included 932 616 patients, of whom 170 482 (18%) had COPD. With respect to association with risk of death, COPD had a partially adjusted hazard ratio (HR) of 1.61 (95% confidence interval [CI] 1.58–1.64), and a fully adjusted HR of 1.26 (95% CI 1.24–1.29). With respect to impact on health system costs, COPD was associated with a partially adjusted relative increase of 13.1% (95% CI 12.7%–13.4%), and an increase of 4.6% (95% CI 4.3%–5.0%) with full adjustment. Frailty, cancer and procedure type (such as orthopedic and lower abdominal surgery) modified the association between COPD and outcomes.Interpretation:Patients with COPD have decreased survival and increased costs in the year after surgery. Frailty, cancer and the type of surgical procedure modified associations between COPD and outcomes, and must be considered when risk-stratifying surgical patients with COPD.Contemporary estimates suggest that more than 10% of surgical patients have COPD.1 Patients with COPD are at increased risk for complications and death within 30 days after surgery;2–4 previous work estimates a 35% increase in odds of morbidity and a 30% increase in odds of death attributable to COPD after risk adjustment.3 However, existing studies have substantial shortcomings. Several included select hospitals, which limits generalizability, while others were narrow in scope and studied selected surgical procedures; most did not follow up patients for more than 30 days after surgery.2–7Patients with COPD may be at increased risk over the longer term owing to age and other comorbidities.8,9 Understanding the longer-term outcomes of surgical patients with COPD is critically important to accurately guide informed consent discussions and project care needs. The costs to health systems to care for patients with COPD after surgery are also unknown;10 delineating these costs would facilitate system-level budgeting and resource allocation. We sought to compare survival and health care costs up to 1 year after inpatient elective surgery between patients with and without COPD in a large, real-world surgical population in a health system where hospital and physician care are government-funded. 相似文献
72.
73.
P. Ramachandra Raju K. Mangapathi Rao S. S. Ganti N. Kalyanasundaram 《Hydrobiologia》1975,46(2-3):199-206
Effects of salinity conditions, ranging from fresh water to 80, on the survival of marine molluscan fouling species, Mytilopsis sallei Recluz, have been studied in the laboratory. The results show that the species exhibits a wide tolerance to different salinity conditions including freshwater, showing normal activity up to 50 beyond which the higher salt concentration had a lethal effect. The effect of various salinity conditions on spawning has also been examined. The significance of wide range tolerance to salinity on the fouling in seawater cooling systems is discussed. 相似文献
74.
Andrea Sankar 《American anthropologist》2003,105(3):638-639
Medical Anthropology and African American Health. Eric J. Bailey. Westport, CT: Berginand Garvey, 2000.255 pp. 相似文献
75.
Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1) 总被引:1,自引:1,他引:0
The mammalian abasic-endonuclease1/redox-factor1 (APE1/Ref1) is an essential protein whose subcellular distribution depends on the cellular physiological status. However, its nuclear localization signals have not been studied in detail. We examined nuclear translocation of APE1, by monitoring enhanced green fluorescent protein (EGFP) fused to APE1. APE1's nuclear localization was significantly decreased by deleting 20 amino acid residues from its N-terminus. Fusion of APE1's N-terminal 20 residues directed nuclear localization of EGFP. An APE1 mutant lacking the seven N-terminal residues (ND7 APE1) showed nearly normal nuclear localization, which was drastically reduced when the deletion was combined with the E12A/D13A double mutation. On the other hand, nearly normal nuclear localization of the full-length E12A/D13A mutant suggests that the first 7 residues and residues 8–13 can independently promote nuclear import. Both far-western analyses and immuno-pull-down assays indicate interaction of APE1 with karyopherin alpha 1 and 2, which requires the 20 N-terminal residues and implicates nuclear importins in APE1's nuclear translocation. Nuclear accumulation of the ND7 APE1(E12A/D13A) mutant after treatment with the nuclear export inhibitor leptomycin B suggests the presence of a previously unidentified nuclear export signal, and the subcellular distribution of APE1 may be regulated by both nuclear import and export. 相似文献
76.
Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Soosairajah J Maiti S Wiggan O Sarmiere P Moussi N Sarcevic B Sampath R Bamburg JR Bernard O 《The EMBO journal》2005,24(3):473-486
Slingshot (SSH) phosphatases and LIM kinases (LIMK) regulate actin dynamics via a reversible phosphorylation (inactivation) of serine 3 in actin-depolymerizing factor (ADF) and cofilin. Here we demonstrate that a multi-protein complex consisting of SSH-1L, LIMK1, actin, and the scaffolding protein, 14-3-3zeta, is involved, along with the kinase, PAK4, in the regulation of ADF/cofilin activity. Endogenous LIMK1 and SSH-1L interact in vitro and co-localize in vivo, and this interaction results in dephosphorylation and downregulation of LIMK1 activity. We also show that the phosphatase activity of purified SSH-1L is F-actin dependent and is negatively regulated via phosphorylation by PAK4. 14-3-3zeta binds to phosphorylated slingshot, decreases the amount of slingshot that co-sediments with F-actin, but does not alter slingshot activity. Here we define a novel ADF/cofilin phosphoregulatory complex and suggest a new mechanism for the regulation of ADF/cofilin activity in mediating changes to the actin cytoskeleton. 相似文献
77.
The neuropeptide galanin suppresses seizure activity in the hippocampus by inhibiting glutamatergic neurotransmission. Galanin may also modulate limbic seizures through interaction with other neurotransmitters in neuronal populations that project to the hippocampus. We examined the role of galanin receptors types 1 and 2 in the dorsal raphe (DR) in the regulation of serotonergic transmission and limbic seizures. Infusion of a mixed agonist of galanin receptors types 1 and 2 [galanin (1-29)] into the DR augmented the severity of limbic seizures in both rats and wild-type mice and concurrently reduced serotonin concentration in the DR and hippocampus as measured by immunofluorescence or HPLC. In contrast, injection of the galanin receptor type 2 agonist galanin (2-11) mitigated the severity of seizures in both species and increased serotonin concentration in both areas. Injection of both galanin fragments into the DR of galanin receptor type 1 knockout mice exerted anticonvulsant effects. Both the proconvulsant activity of galanin (1-29) and seizure suppression by galanin (2-11) were abolished in serotonin-depleted animals. Our data indicate that, in the DR, galanin receptors types 1 and 2 modulate serotonergic transmission in a negative and a positive fashion, respectively, and that these effects translate into either facilitation or inhibition of limbic seizures. 相似文献
78.
79.
80.
Several strategies for mapping ventricular outflow tract tachycardia have been reported as useful indices for differentiating between those originating from the right and the left side. Recently, tissue tracking imaging (TTI) has been demonstrated as a novel non-invasive modality for identifying the origin of outflow tract tachycardias. Tissue tracking imaging is an ultrasonographic technique that measures the myocardial motion amplitude towards the transducer in each region during systole, identifying regional myocardial displacement on the basis of myocardial velocities using color Doppler myocardial imaging principles. In this technique, the origin of the arrhythmia could be recognized as the site where the earliest color-coded signal (ECCS) appeared on the myocardium at the onset of the systole. In preliminary studies this modality was found to be useful in differentiating outflow tract ventricular tachycardias. ECCS was always found below or at the level of the pulmonary valve in all arrhythmias which could be ablated from the right ventricular outflow tract, while in those where the ECCS was above and close to the pulmonary valve it could be ablated from the left sinus of valsalva. These results indicate that TTI can provide detailed and accurate information on the arrhythmia origin of outflow tract tachycardia and may be useful for differentiating between an outflow tract tachycardia originating from the LV epicardium remote from the LSV and that from the LSV. Newer advances in echocardiographic technologies like high resolution, high frame rate real time three dimensional echocardiography with speckle tracking may further improve the precise localization of arrhythmias in the future. 相似文献