全文获取类型
收费全文 | 2655篇 |
免费 | 216篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 21篇 |
儿科学 | 114篇 |
妇产科学 | 52篇 |
基础医学 | 471篇 |
口腔科学 | 19篇 |
临床医学 | 253篇 |
内科学 | 597篇 |
皮肤病学 | 68篇 |
神经病学 | 210篇 |
特种医学 | 62篇 |
外科学 | 391篇 |
综合类 | 10篇 |
一般理论 | 1篇 |
预防医学 | 141篇 |
眼科学 | 28篇 |
药学 | 190篇 |
中国医学 | 9篇 |
肿瘤学 | 242篇 |
出版年
2023年 | 10篇 |
2022年 | 15篇 |
2021年 | 57篇 |
2020年 | 42篇 |
2019年 | 52篇 |
2018年 | 66篇 |
2017年 | 53篇 |
2016年 | 50篇 |
2015年 | 54篇 |
2014年 | 91篇 |
2013年 | 113篇 |
2012年 | 180篇 |
2011年 | 202篇 |
2010年 | 93篇 |
2009年 | 93篇 |
2008年 | 159篇 |
2007年 | 166篇 |
2006年 | 154篇 |
2005年 | 120篇 |
2004年 | 156篇 |
2003年 | 136篇 |
2002年 | 105篇 |
2001年 | 48篇 |
2000年 | 47篇 |
1999年 | 55篇 |
1998年 | 41篇 |
1997年 | 19篇 |
1996年 | 18篇 |
1995年 | 26篇 |
1994年 | 21篇 |
1992年 | 37篇 |
1991年 | 28篇 |
1990年 | 27篇 |
1989年 | 27篇 |
1988年 | 31篇 |
1987年 | 25篇 |
1986年 | 24篇 |
1985年 | 20篇 |
1984年 | 20篇 |
1983年 | 18篇 |
1982年 | 10篇 |
1981年 | 13篇 |
1980年 | 15篇 |
1979年 | 29篇 |
1977年 | 9篇 |
1974年 | 15篇 |
1973年 | 11篇 |
1972年 | 15篇 |
1971年 | 9篇 |
1969年 | 9篇 |
排序方式: 共有2879条查询结果,搜索用时 855 毫秒
91.
Yong-Jie Zhang Karen Jansen-West Ya-Fei Xu Tania F. Gendron Kevin F. Bieniek Wen-Lang Lin Hiroki Sasaguri Thomas Caulfield Jaime Hubbard Lillian Daughrity Jeannie Chew Veronique V. Belzil Mercedes Prudencio Jeannette N. Stankowski Monica Castanedes-Casey Ena Whitelaw Peter E. A. Ash Michael DeTure Rosa Rademakers Kevin B. Boylan Dennis W. Dickson Leonard Petrucelli 《Acta neuropathologica》2014,128(4):505-524
The occurrence of repeat-associated non-ATG (RAN) translation, an atypical form of translation of expanded repeats that results in the synthesis of homopolymeric expansion proteins, is becoming more widely appreciated among microsatellite expansion disorders. Such disorders include amyotrophic lateral sclerosis and frontotemporal dementia caused by a hexanucleotide repeat expansion in the C9ORF72 gene (c9FTD/ALS). We and others have recently shown that this bidirectionally transcribed repeat is RAN translated, and the “c9RAN proteins” thusly produced form neuronal inclusions throughout the central nervous system of c9FTD/ALS patients. Nonetheless, the potential contribution of c9RAN proteins to disease pathogenesis remains poorly understood. In the present study, we demonstrate that poly(GA) c9RAN proteins are neurotoxic and may be implicated in the neurodegenerative processes of c9FTD/ALS. Specifically, we show that expression of poly(GA) proteins in cultured cells and primary neurons leads to the formation of soluble and insoluble high molecular weight species, as well as inclusions composed of filaments similar to those observed in c9FTD/ALS brain tissues. The expression of poly(GA) proteins is accompanied by caspase-3 activation, impaired neurite outgrowth, inhibition of proteasome activity, and evidence of endoplasmic reticulum (ER) stress. Of importance, ER stress inhibitors, salubrinal and TUDCA, provide protection against poly(GA)-induced toxicity. Taken together, our data provide compelling evidence towards establishing RAN translation as a pathogenic mechanism of c9FTD/ALS, and suggest that targeting the ER using small molecules may be a promising therapeutic approach for these devastating diseases. 相似文献
92.
An individual rehabilitation program: Evaluation by Parkinsonian patients and their physiotherapists
F. Ory Magne N. Fabre C. Gu C. Pastorelli S. Tardez J.-C. Marchat P. Marque C. Brefel Courbon 《Revue neurologique》2014
Objectives
The purpose of this work was to study the feasibility of an individual Parkinson disease (PD) rehabilitation program based on each patient's prevalent symptoms and to determine the effects of this program on patient's quality of life as well as the level of patient's and physiotherapist's satisfaction with the program.Patients and methods
In association with physiotherapists with expertise in PD, a physical medicine and rehabilitation physician, we elaborated a physical therapy program based on the core areas for physical therapy in PD: transfers; posture; balance and falls; physical capacity and inactivity. Within this program, we selected exercises tailored to each patient's main impairment and proposed this selection to their local physiotherapist for three months. Quality of life was evaluated with PDQ-39 at baseline and after three months of the individualized physical therapy program. We built an anonymous satisfaction questionnaire for patients and physiotherapists that was filled out at the end of the program.Results
One hundred and three individuals with moderately advanced but clinically stable idiopathic PD were included. Significant improvement was found for the emotional well-being, bodily discomfort and stigma domain (P ≤ 0.05). No significant improvement was found for the other PDQ-39 domains. The mean global satisfaction figures for this program were 6.0 ± 2.4 and 7.2 ± 2.1 for patients and physiotherapists respectively. Most of the patients felt improved by the physiotherapy program and especially for transfer, balance, gait, and mobility.Conclusion
Our study found evidence of the potential benefits of a patient-tailored physiotherapy program. Such a program was feasible and had a favorable impact on patients’ quality of life and on physiotherapists’ practices for PD patients. Specific physiotherapy may be effective to limit physical mobility impairment. Our results also pointed out that physiotherapy may be efficient to confine the negative impact of social isolation, pain and emotional reactions. Such a program should be associated with a therapeutic education intervention such as encouraging patients to perform physical therapy exercises alone. 相似文献93.
Toplak N Frenkel J Ozen S Lachmann HJ Woo P Koné-Paut I De Benedetti F Neven B Hofer M Dolezalova P Kümmerle-Deschner J Touitou I Hentgen V Simon A Girschick H Rose C Wouters C Vesely R Arostegui J Stojanov S Ozgodan H Martini A Ruperto N Gattorno M;Paediatric Rheumatology International Trials Organisation 《Annals of the rheumatic diseases》2012,71(7):1177-1182
94.
Microscopic evaluation of induced tooth movement in traumatized teeth: an experimental study in rats
Alex Luiz Pozzobon Pereira Marcos Rogério de Mendonça Celso Koogi Sonoda Mauro Carlos Agner Bussato Osmar Aparecido Cuoghi Aubrey Fernando Fabre 《Dental traumatology》2012,28(2):114-120
Abstract – The clinical management of orthodontic patients with dental trauma before or during the treatment is mainly founded on clinical experience, expert opinions, and individual case reports. It is proposed in the literature that teeth sustaining mild trauma with minor damage to the periodontium (e.g. subluxation) should be followed for a period of time before being subjected to orthodontic forces. A minimum period of 3 months has been proposed. In this study, we used an animal model to investigate whether shorter observation periods could be established in case of mild trauma. The periradicular region of rat molars was examined microscopically to determine the biological events of tooth movement started 15 and 30 days after intentional subluxation using an experimental method to induce dentoalveolar trauma. Thirty adult male Wistar rats were assigned to 6 groups (n = 5): Group 1 (control – no trauma/orthodontic movement); Group 2: the animals received an orthodontic device and were sacrificed after 7 days; Groups 3 and 4: dentoalveolar trauma (subluxation) was experimentally induced by the application of an axial force of 900 cN on the occlusal surface of the maxillary right first molar, and the animals were sacrificed after 22 and 37 days, respectively; and Groups 5 and 6: 15 and 30 days, respectively, after force application, an orthodontic device was installed and the rats were sacrificed 7 days later. In G5 and G6, the periodontal ligament and pulp tissue were rich in cellular elements and blood vessels, the alveolar bone was preserved, and the root surface presented only very small areas of surface resorption (cementum), maintaining the characteristics of normality. In conclusion, the microscopic alterations in the gingival and periodontal tissues in response to an experimentally induced mild dentoalveolar trauma simulating subluxation were not sufficient to contraindicate starting the orthodontic movement 15 and 30 days after trauma. 相似文献
95.
Ohtani T Mohammed SF Yamamoto K Dunlay SM Weston SA Sakata Y Rodeheffer RJ Roger VL Redfield MM 《European heart journal》2012,33(14):1742-1749
96.
Background: The decline in skeletal muscle in old age is a factor in the development of functional limitations. Objective: The objective of this study was to assess if there is a correlation between muscle mass based on bioelectrical impedance analysis (BIA) detection and the fall incidence in nursing home residents and to examine the risk factors for falling in nursing home residents. Methods: This prospective cohort study was part of a longitudinal study on nutritional issues in 52 nursing homes in Antwerp (Belgium) from October 2007 to April 2008. Two hundred and seventy-six people aged 65 years and older were included. Each subject was assessed with BIA, the timed get-up-and-go test, the Katz score, the Mini Nutritional Assessment - Short Form and the 36-Item Short Form Health Survey. The primary outcome parameter was fall incidence during the study. Results: The prevalence of sarcopenia varied from 24.3 to 81.5% depending on which definition was used. No association was found between BIA-derived muscle mass and fall incidence. Logistic regression analysis showed that gait speed (odds ratio 1.029; p = 0.003) and mental health (odds ratio 0.981; p = 0.015) are significantly associated with fall incidence in nursing homes. A receiver operating characteristic curve showed that none of the BIA-derived muscle parameters are good predictors of the risk of falling. Conclusions: This study shows that there is no association between sarcopenia based on BIA and fall incidence and that BIA-derived muscle mass has no additional value in predicting fall incidents compared to the timed get-up-and-go test. 相似文献
97.
Fabre C Koscielny S Mohty M Fegueux N Blaise D Maillard N Tabrizi R Michallet M Socié G Yakoub-Agha I Garban F Uzunov M François S Contentin N Lapusan S Bourhis JH 《Haematologica》2012,97(4):482-490
Background
How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).Design and Methods
This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.Results
Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.Conclusions
We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies. 相似文献98.
Kong MC Nahata MC Lacombe VA Seiber EE Balkrishnan R 《Journal of general internal medicine》2012,27(9):1159-1164
Background
Racial disparities exist in many aspects of HIV/AIDS. Comorbid depression adds to the complexity of disease management. However, prior research does not clearly show an association between race and antiretroviral therapy (ART) adherence, or depression and adherence. It is also not known whether the co-existence of depression modifies any racial differences that may exist.Objective
To examine racial differences in ART adherence and whether the presence of comorbid depression moderates these differences among Medicaid-enrolled HIV-infected patients.Design
Retrospective cohort study.Setting
Multi-state Medicaid database (Thomson Reuters MarketScan®).Participants
Data for 7,034 HIV-infected patients with at least two months of antiretroviral drug claims between 2003 and 2007 were assessed.Main Measures
Antiretroviral therapy adherence (90 % days covered) were measured for a 12-month period. The main independent variables of interest were race and depression. Other covariates included patient variables, clinical variables (comorbidity and disease severity), and therapy-related variables.Key Results
In this study sample, over 66 % of patients were of black race, and almost 50 % experienced depression during the study period. A significantly higher portion of non-black patients were able to achieve optimal adherence (≥90 %) compared to black patients (38.6 % vs. 28.7 %, p < 0.001). In fact, black patients had nearly 30 % decreased odds of being optimally adherent to antiretroviral drugs compared to non-black patients (OR = 0.70, 95 % CI: 0.63–0.78), and was unchanged regard less of whether the patient had depression. Antidepressant treatment nearly doubled the odds of optimal ART adherence among patients with depression (OR = 1.92, 95 % CI: 1.12–3.29).Conclusions
Black race was significantly associated with worse ART adherence, which was not modified by the presence of depression. Under-diagnosis and under-treatment of depression may hinder ART adherence among HIV-infected patients of all races.KEY WORDS: HIV, adherence, depression, race, Medicaid 相似文献99.
Dougados M Braun J Szanto S Combe B Geher P Leblanc V Logeart I 《Rheumatology (Oxford, England)》2012,51(9):1687-1696
Objective. To evaluate the longer-term efficacy of etanercept in patients with severe and advanced active AS. Methods. Seventy-seven patients who completed the randomized, double-blind, placebo-controlled 12-week SPINE study enrolled in a 12-week open-label extension and received s.c. etanercept 50?mg once weekly. The etanercept/etanercept group received a total of 24 weeks treatment with etanercept (n?=?38); the placebo/etanercept group received placebo during the double-blind study then 12 weeks' etanercept treatment during the open-label extension (n?=?39). Results. At the end of the open-label extension, BASDAI scores in the etanercept/etanercept group had further decreased beyond reductions observed during the double-blind study [mean (s.d.) change from baseline -37.6 (22.4) at end of extension vs -27.4 (23.8) at end of double-blind study]. Mean (s.d.) BASDAI scores also improved in the placebo/etanercept group once switched to etanercept [-28.6 (24.3) vs -15.0 (20.0)]. Similar trends were observed in BASFI and BASMI scores. In the placebo/etanercept group, total back pain decreased to similar levels achieved in the etanercept group in the double-blind study. Pain levels continued to decrease with longer-term etanercept therapy in the etanercept/etanercept group. Conclusion. Despite the improvements in symptoms and inflammatory markers observed shortly after initiation of once-weekly etanercept, there was no notable plateauing effect on patient-reported outcomes. Indeed, signs and symptoms of severe and advanced active AS continued to improve after up to 24 weeks, treatment with etanercept. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov/ct2/home, NCT00420238. 相似文献
100.
Joan Eilstein Sébastien Grégoire Aurélie Fabre Eric Arbey Camille Géniès Hélène Duplan Helga Rothe Corie Ellison Richard Cubberley Andreas Schepky Daniela Lange Martina Klaric Nicola J. Hewitt Carine Jacques-Jamin 《Journal of applied toxicology : JAT》2020,40(3):416-433
The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients. 相似文献