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11.
Anita Nguyen Hartzell V. Schaff Dustin Hang Rick A. Nishimura Jeffrey B. Geske Joseph A. Dearani Brian D. Lahr Steve R. Ommen 《The Journal of thoracic and cardiovascular surgery》2019,157(1):306-315.e3
Objectives
In patients with hypertrophic cardiomyopathy, obstruction of the left ventricular outflow tract can be relieved by surgical septal myectomy or alcohol septal ablation, but uncertainty remains regarding long-term results and comparative effectiveness of alcohol septal ablation. This study aims to compare short- and long-term outcomes of the 2 procedures.Methods
Between December 1998 and September 2016, 2407 patients underwent septal myectomy and 211 patients underwent alcohol septal ablation at our institution. After 2:1 propensity score matching, the study cohort included 334 patients who underwent myectomy and 167 patients who underwent alcohol septal ablation.Results
Median (interquartile range) ages of patients in the myectomy and alcohol septal ablation groups were 65 (58-71) years and 64 (56-73) years (P = .9), respectively. After intervention, median resting left ventricular outflow tract gradient at predischarge transthoracic echocardiography was 0 (0-10) mm Hg in the myectomy group (n = 288) and 21 (10-60) mm Hg in the alcohol septal ablation group (n = 63) (P < .001, tested at baseline gradients of 30 and 50 mm Hg). There were no differences in survival between the 2 groups (risk of death for alcohol septal ablation vs myectomy, hazard ratio, 1.5; 95% confidence interval, 0.9-2.6; P = .1). Survival of patients undergoing septal myectomy was better than that of an age-, sex-, and race-matched US population (82% vs 75% at 12 years, P = .01). Reintervention for left ventricular outflow tract obstruction was more likely to occur in patients who received alcohol septal ablation (hazard ratio, 33.3; 95% confidence interval, 4.4-250.6; P < .001).Conclusions
There were no differences in survival of patients undergoing myectomy or alcohol septal ablation, but freedom from reintervention and early and late reduction of left ventricular outflow tract gradient are superior in patients undergoing septal myectomy. 相似文献12.
13.
Ayla Gunlemez Canan Baydemir Ayse Arisoy 《The journal of maternal-fetal & neonatal medicine》2019,32(14):2412-2417
Objective: Late-preterm delivery is known to be associated with potential adverse effects on lung development. Passive smoking may result in alterations of pulmonary function in infants born late-preterm. Impulse oscillometry (IOS) is a noninvasive, rapid, and practicable technique that can assess lung function. This study aimed to evaluate the effect of passive smoking on lung function tests in preschool children born late-preterm using IOS.Methods: The study population consisted of a total of 139 children between 3 and 7 years of age born late-preterm who were being followed-up at our outpatient unit at the time of study period. Late-preterms were subcategorized according to presence or absence of exposure to passive smoking (PS). Those with and without exposure to passive smoking were referred to as PS group (56.1%, n?=?78) and non-PS group (43.9%, n?=?61), respectively. Resistance (R5–R20), reactance (X5–X20), and resonant frequency were measured by impulse oscillometry (IOS) at 5–20?Hz.Results: Median R5-R20 and Z5 were significantly higher and median X10 was significantly lower in PS group compared to non-PS group (p?.05).Conclusions: This study demonstrated that passive smoking significantly increases peripheral airway resistance and seems to adversely affect lung function in children born late-preterm. 相似文献
14.
D. J. Roberts K. Sanok H. Chen M. Chan P. Yurt A. K. Thakur G. L. DeVito H. Murli L. F. Stankowski Jr. 《Environmental and molecular mutagenesis》2012,53(4):297-303
A flow cytometric procedure for determining mitotic index (MI) as part of the metaphase chromosome aberrations assay, developed and utilized routinely at Pfizer as part of their standard assay design, has been adopted successfully by Covance laboratories. This method, using antibodies against phosphorylated histone tails (H3PS10) and nucleic acid stain, has been evaluated by the two independent test sites and compared to manual scoring. Primary human lymphocytes were treated with cyclophosphamide, mitomycin C, benzo(a)pyrene, and etoposide at concentrations inducing dose‐dependent cytotoxicity. Deming regression analysis indicates that the results generated via flow cytometry (FCM) were more consistent between sites than those generated via microscopy. Further analysis using the Bland–Altman modification of the Tukey mean difference method supports this finding, as the standard deviations (SDs) of differences in MI generated by FCM were less than half of those generated manually. Decreases in scoring variability owing to the objective nature of FCM, and the greater number of cells analyzed, make FCM a superior method for MI determination. In addition, the FCM method has proven to be transferable and easily integrated into standard genetic toxicology laboratory operations. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc. 相似文献
15.
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of ∼850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses. 相似文献
16.
Patrick J. Cimino Yue Yang Xianwu Li Jake F. Hemingway Makenzie K. Cherne Shawn B. Khademi Yoshinori Fukui Kathleen S. Montine Thomas J. Montine C. Dirk Keene 《Experimental and molecular pathology》2013
Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2 −/−), were hemizygous for DOCK2 (DOCK2 +/−), or that expressed two DOCK2 genes (DOCK2 +/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2 −/− mice compared with APPswe-PS1Δe9/DOCK2 +/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD. 相似文献
17.
Jack Rivers-Auty Victor S. Tapia Claire S. White Michael J.D. Daniels Samuel Drinkall Paul T. Kennedy Harry G. Spence Shi Yu Jack P. Green Christopher Hoyle James Cook Amy Bradley Alison E. Mather Ruth Peters Te-Chen Tzeng Margaret J. Gordon John H. Beattie David Brough Catherine B. Lawrence 《The Journal of neuroscience》2021,41(13):3025
Alzheimer''s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer''s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer''s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer''s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer''s disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer''s-like memory deficits without modifying amyloid β plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer''s disease.SIGNIFICANCE STATEMENT Alzheimer''s disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer''s disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer''s disease; thus, we hypothesized that zinc status would affect Alzheimer''s disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer''s disease. In an animal model of Alzheimer''s disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer''s disease progression, and that zinc supplementation could slow the rate of cognitive decline. 相似文献
18.
Dong Liu Ismayil Ahmet Brandon Griess David Tweedie Nigel H Greig Mark P Mattson 《Journal of cerebral blood flow and metabolism》2021,41(7):1579
Local cerebral blood flow (CBF) responses to neuronal activity are essential for cognition and impaired CBF responses occur in Alzheimer’s disease (AD). In this study, regional CBF (rCBF) responses to the KATP channel opener diazoxide were investigated in 3xTgAD, WT and mutant Presenilin 1(PS1M146V) mice from three age groups using Laser-Doppler flowmetry. The rCBF response was reduced early in young 3xTgAD mice and almost absent in old 3xTgAD mice, up to 30%–40% reduction with altered CBF velocity and mean arterial pressure versus WT mice. The impaired rCBF response in 3xTgAD mice was associated with progression of AD pathology, characterized by deposition of intracellular and vascular amyloid-β (Aβ) oligomers, senile plaques and tau pathology. The nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine abolished rCBF response to diazoxide suggesting NO was involved in the mediation of vasorelaxation. Levels of phosphor-eNOS (Ser1177) diminished in 3xTgAD brains with age, while the rCBF response to the NO donor sodium nitroprusside remained. In PS1M146V mice, the rCBF response to dizoxide reduced and high molecular weight Abeta oligomers were increased indicating PS1M146V contributed to the dysregulation of rCBF response in AD mice. Our study revealed an Aβ oligomer-associated compromise of cerebrovascular function in rCBF response to diazoxide in AD mice with PS1M146V mutation. 相似文献
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20.
Eric Y. Wong Cally A. Jennings Wendy M. Rodgers Anne-Marie Selzler Lindsay G. Simmonds Rashida Hamir Michael K. Stickland 《Patient education and counseling》2014