全文获取类型
收费全文 | 833篇 |
免费 | 38篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 16篇 |
妇产科学 | 28篇 |
基础医学 | 124篇 |
口腔科学 | 9篇 |
临床医学 | 51篇 |
内科学 | 169篇 |
皮肤病学 | 10篇 |
神经病学 | 74篇 |
特种医学 | 10篇 |
外科学 | 72篇 |
综合类 | 8篇 |
预防医学 | 96篇 |
眼科学 | 14篇 |
药学 | 142篇 |
肿瘤学 | 51篇 |
出版年
2023年 | 4篇 |
2022年 | 25篇 |
2021年 | 69篇 |
2020年 | 18篇 |
2019年 | 26篇 |
2018年 | 41篇 |
2017年 | 24篇 |
2016年 | 24篇 |
2015年 | 14篇 |
2014年 | 28篇 |
2013年 | 34篇 |
2012年 | 78篇 |
2011年 | 78篇 |
2010年 | 30篇 |
2009年 | 25篇 |
2008年 | 47篇 |
2007年 | 45篇 |
2006年 | 41篇 |
2005年 | 46篇 |
2004年 | 39篇 |
2003年 | 31篇 |
2002年 | 23篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1981年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有879条查询结果,搜索用时 31 毫秒
1.
Stefan Scholz Florian Koerber Kinga Meszaros Rosa Maya Fassbender Bernhard Ultsch Robert R. Welte Wolfgang Greiner 《Vaccine》2019,37(12):1692-1701
Introduction
Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.Method
A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.Results
The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case.Discussion
The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous. 相似文献2.
Rachel P. Winograd Ned Presnall Erin Stringfellow Claire Wood Phil Horn Alex Duello 《The American journal of drug and alcohol abuse》2019,45(4):333-340
Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD. 相似文献
3.
F Elferink W J van der Vijgh W W ten Bokkel Huinink J B Vermorken I Klein B Winograd M K Knobf G Simonetti H E Gall J G McVie 《British journal of cancer》1987,56(4):479-483
Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin. 相似文献
4.
Acute phase response following total hip replacement and in patients with aseptic loosening] 总被引:1,自引:0,他引:1
Jacek Markuszewski Ma?gorzata Wierusz-Koz?owska Waldemar Wo?niak Kinga Le?niewska Magdalena Sobieska 《Chirurgia narzadów ruchu i ortopedia polska》2007,72(5):305-309
INTRODUCTION: Aseptic loosening is a result of the chronic inflammatory reaction in periprosthetic tissues. Its intensity depends on the implants construction material and reactivity of the host's tissues. The aim of the study was the evaluation of the acute phase proteins in various periods following total hip replacement and comparison between acute phase response observed in patients with well-functioning implants and with aseptic loosening. MATERIAL: The study group consisted of 97 patients following THR due to the hip osteoarthritis. Patients of Group I were evaluated before the surgery and 6 months after primary THR. Group II consisted of patients 3-4 years after primary THR. Group consisted of patients with aseptic loosening. Patients of all groups were divided according to the implant type (cemente/uncemented). METHODS: Concentrations of evaluated acute phase proteins: C-reactive protein (CRP), transferrin (Tf) and alpha-glycoprotein were assessed using immunoelectrophoresis. RESULTS: In vast majority of patients (71-95%) following THR had present w3 variant of AGP which should be negative in physiological conditions. The average concentrations of AGP and AGP-RC were higher in patients following cemented THR. CONCLUSIONS: Implantation of the endoprosthesis raises a chronic inflammatory reaction expressed by changes in the profiles of acute phase proteins. This process is more visible in patients following cemented THR. The profiles of the acute phase proteins in patients with aseptic loosening were not different than those observed in patients with well-functioning implants, what makes them useless as a diagnostic tool for loosening. This lack of differences may be caused by adaptation of the generalised response to long lasting process of aseptic loosening 相似文献
5.
The mere exposure effect was examined in patients with mild to moderate Alzheimer's disease (AD). Twenty patients and 20 elderly controls judged the physical characteristics of faces. Implicit memory was tested later by presenting pairs of faces (old and new) and asking participants which faces they liked better. Patients and controls exhibited above chance preference for previously exposed faces. Experiment 2 evaluated whether the preserved implicit memory of patients was mediated by explicit memory. Patients and controls again judged faces but then later chose which faces they had seen before. Patients exhibited impaired recognition memory compared to controls. These findings suggest that a mere exposure effect for unfamiliar faces is present in mild to moderate AD. The results are discussed in terms of perceptual and conceptual priming and relatively spared occipital lobe functioning in early AD. 相似文献
6.
Pleiotropic control of glucose and hormone responses by PRL1, a nuclear WD protein, in Arabidopsis 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Genes & development》网站下载免费的PDF全文](/ch/ext_images/free.gif)
7.
The Topography of Non-Linear Cortical Dynamics at Rest, in Mental Calculation and Moving Shape Perception 总被引:3,自引:0,他引:3
Andreas Meyer-Lindenberg Ulrike Bauer Stefan Krieger Stefanie Lis Kinga Vehmeyer Georg Schüler Bernd Gallhofer 《Brain topography》1998,10(4):291-299
Differential cortical activation by cognitive processing was studied using dimensional complexity, a measure derived from nonlinear dynamics that indicates the degrees of freedom (complexity) of a dynamic system. We examined the EEG of 32 healthy subjects at rest, during a visually presented calculation task, and during a moving shape perception task. As a nonlinear measure of connectivity, the mutual dimension of selected electrode pairs was used. The first Lyapunov coefficient was also calculated. Data were tested for non-linearity using a surrogate data method and compared to spectral EEG measures (power, coherence). Surrogate data testing confirmed the presence of nonlinear structure in the data. Cognitive activation led to a highly significant rise in dimensional complexity. While both tasks activated central, parietal and temporal areas, mental arithmetic showed frontal activation and an activity maximum at T3, while the moving shape task led to occipital activation and a right parietal activity maximum. Analysis of mutual dimension showed activation of a bilateral temporal-right frontal network in calculation. The Lyapunov coefficent showed clear topographic variation, but was not significantly changed by mental tasks (p<.09). While dimensional complexity was almost unrelated to power values, nonlinear (mutual dimension) and linear (coherence) measures of connectivity shared up to 37% of variance. Data are interpreted in terms of increased cortical complexity as a result of recruitment of asynchronously active, distributed neuronal assemblies in cognition. The topography of nonlinear dynamics are related to neuropsychological and neuroimaging findings on mental calculation and moving shape perception. 相似文献
8.
The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding. The adhesive properties of the DIDS binding region (DBR) was demonstrated by competition experiments using synthetic peptides and by direct interaction of such peptides with CD36 transfected CHO cells. The results suggest that host membrane proteins such as AE1 contribute to the adhesion of malaria-infected erythrocytes to CD36. 相似文献
9.
Johnson TS Xu JW Zaporojan VV Mesa JM Weinand C Randolph MA Bonassar LJ Winograd JM Yaremchuk MJ 《Tissue engineering》2004,10(9-10):1308-1315
Articular chondrocytes can synthesize new cartilaginous matrix in vivo that forms functional bonds with native cartilage. Other sources of chondrocytes may have a similar ability to form new cartilage with healing capacity. This study evaluates the ability of various chondrocyte sources to produce new cartilaginous matrix in vivo and to form functional bonds with native cartilage. Disks of articular cartilage and articular, auricular, and costal chondrocytes were harvested from swine. Articular, auricular, or costal chondrocytes suspended in fibrin glue (experimental), or fibrin glue alone (control), were placed between disks of articular cartilage, forming trilayer constructs, and implanted subcutaneously into nude mice for 6 and 12 weeks. Specimens were evaluated for neocartilage production and integration into native cartilage with histological and biomechanical analysis. New matrix was formed in all experimental samples, consisting mostly of neocartilage integrating with the cartilage disks. Control samples developed fibrous tissue without evidence of neocartilage. Ultimate tensile strength values for experimental samples were significantly increased (p < 0.05) from 6 to 12 weeks, and at 12 weeks they were significantly greater (p < 0.05) than those of controls. We conclude that articular, auricular, and costal chondrocytes have a similar ability to produce new cartilaginous matrix in vivo that forms mechanically functional bonds with native cartilage. 相似文献
10.
ukasz Kopiasz Katarzyna Dziendzikowska Magorzata Gajewska Micha Oczkowski Kinga Majchrzak-Kuligowska Tomasz Krlikowski Joanna Gromadzka-Ostrowska 《Nutrients》2021,13(2)
Background: Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model. Methods: A total of 150 Sprague–Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG−) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot. Results: The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days. Conclusions: Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD. 相似文献