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101.
Charlotte W Ockeloen Marjolein H Willemsen Sonja de Munnik Bregje WM van Bon Nicole de Leeuw Aad Verrips Sarina G Kant Elizabeth A Jones Han G Brunner Rosa LE van Loon Eric EJ Smeets Mieke M van Haelst Gijs van Haaften Ann Nordgren Helena Malmgren Giedre Grigelioniene Sascha Vermeer Pedro Louro Lina Ramos Thomas JJ Maal Celeste C van Heumen Helger G Yntema Carine EL Carels Tjitske Kleefstra 《European journal of human genetics : EJHG》2015,23(9):1270-1185
Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases. 相似文献
102.
103.
Elizabeth E. Tolley Jamilah Taylor Allison Pack Elizabeth Greene Jill Stanton Victoria Shelus Richard Dunner Theo Hodge Bernard Branson Wafaa M. El-Sadr Theresa Gamble 《AIDS and behavior》2018,22(1):245-257
The stages of change (SOC) theory suggests individuals adapt incrementally to behaviors like adherence, requiring different strategies over the behavior change continuum. Offering financial incentives (FIs) is one strategy to motivate adherence. This qualitative sub-study examined adherence barriers and the role of FIs to increase viral suppression (VS) among HIV Prevention Trials Network (HPTN) 065 study participants categorized into SOC-related adherence stages based on changes from baseline to follow-up viral load tests. Of 73 participants, most were in Maintenance stage (n = 31), defined as having achieved VS throughout HPTN 065, or in Action stage (n = 29), defined as moving from virally unsuppressed to suppressed in 50% or more of tests. Only 13 were Low Adherers, having achieved VS in fewer than 50% of tests. The latter group faced substantial social and structural adherence barriers. Participants in the Action stage made positive changes to adherence routines to achieve VS. Those in Maintenance were less incentivized by FIs, as they were already committed. Results from this sub-study suggest FI effectiveness may vary across the SOC continuum, with greatest impact for those initiating antiretroviral or without explicit adherence routines. FIs may be insufficient to overcome strong social or structural barriers, and unnecessary for those intrinsically committed to remaining adherent. 相似文献
104.
Judith de Vos-Geelen Sandra ME Geurts Margreet van Putten Liselot BJ Valkenburg-van Iersel Heike I Grabsch Nadia Haj Mohammad Frank JP Hoebers Chantal V Hoge Paul M Jeene Evelien JM de Jong Hanneke WM van Laarhoven Tom Rozema Marije Slingerland Vivianne CG Tjan-Heijnen Grard AP Nieuwenhuijzen Valery EPP Lemmens 《World journal of gastroenterology : WJG》2019,25(47):6835-6846
BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time. 相似文献
105.
De Cock KM El-Sadr WM Ghebreyesus TA 《Journal of acquired immune deficiency syndromes (1999)》2011,57(Z2):S61-S63
Game changers are radical innovations that result in fundamental and durable changes. The global HIV program scale-up witnessed over the past decade has included some innovations that are not well appreciated. The willingness to rapidly adopt and implement innovations, the flexibility and speed of program implementation, and the readiness to re-examine professional roles are just a few of such game changers. However, moving ahead, further work is needed to enhance the quality of programs, to energetically tackle HIV prevention, to build on this success, and to address other health threats that these same communities face. 相似文献
106.
T Ibrahim B Bloch CN Esler KR Abrams WM Harper 《Annals of the Royal College of Surgeons of England》2010,92(3):231-235
INTRODUCTION
The aim of this study was to evaluate temporal trends in the prevalence of primary total hip and knee replacements (THRs and TKRs) throughout the Trent region from 1991 to 2004.PATIENTS AND METHODS
The Trent Regional Arthroplasty Study records details of primary THR and TKR prospectively and data from the register were examined. Age and gender population data were provided by the Office for National Statistics.RESULTS
A total of 26,281 THRs and 23,606 TKRs were recorded during this period. Analysis showed that females had an increased incidence rate ratio (IRR) for both primary THR (IRR = 1.29; 95% CI 1.26–1.33; P < 0.001) and TKR (IRR = 1.17; 95% CI 1.14–1.20; P < 0.001). Patients aged 74–85 years had the largest IRR for both primary THR (IRR = 6.7; 95% CI 6.4–7.0; P < 0.001) and TKR (IRR = 15.3; 95% CI 14.4–16.3; P < 0.001).CONCLUSIONS
The prevalence of primary TKR increased significantly over time whereas THR remained steady in the Trent region between 1991 and 2004. 相似文献107.
Koon H Chan Jason SC Kwan Philip WL Ho Jessica WM Ho Andrew CY Chu David B Ramsden 《Journal of neuroinflammation》2010,7(1):50
Background
Neuromyelitis optica spectrum disorders (NMOSD) are severe central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM) and/or optic neuritis (ON). A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA) and cell-based IIFA. 相似文献108.
Joan Chang Monica M Nicolau Thomas R Cox Daniel Wetterskog John WM Martens Holly E Barker Janine T Erler 《Breast cancer research : BCR》2013,15(4):R67
Introduction
Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expression in normal mammary epithelial cells to gain insight into how LOXL2 mediates cancer progression.Methods
LOXL2 was expressed in MCF10A normal human mammary epithelial cells. The 3D acinar morphogenesis of these cells was assessed, as well as the ability of the cells to form branching structures on extracellular matrix (ECM)-coated surfaces. Transwell-invasion assays were used to assess the invasive properties of the cells. Clinically relevant inhibitors of ErbB2, lapatinib and Herceptin (traztuzumab), were used to investigate the role of ErbB2 signaling in this model. A retrospective study on a previously published breast cancer patient dataset was carried out by using Disease Specific Genomic Analysis (DSGA) to investigate the correlation of LOXL2 mRNA expression level with metastasis and survival of ErbB2-positive breast cancer patients.Results
Fluorescence staining of the acini revealed increased proliferation, decreased apoptosis, and disrupted polarity, leading to abnormal lumen formation in response to LOXL2 expression in MCF10A cells. When plated onto ECM, the LOXL2-expressing cells formed branching structures and displayed increased invasion. We noted that LOXL2 induced ErbB2 activation through reactive oxygen species (ROS) production, and ErbB2 inhibition by using Herceptin or lapatinib abrogated the effects of LOXL2 on MCF10A cells. Finally, we found LOXL2 expression to be correlated with decreased overall survival and metastasis-free survival in breast cancer patients with ErbB2-positive tumors.Conclusions
These findings suggest that LOXL2 expression in normal epithelial cells can induce abnormal changes that resemble oncogenic transformation and cancer progression, and that these effects are driven by LOXL2-mediated activation of ErbB2. LOXL2 may also be a beneficial marker for breast cancer patients that could benefit most from anti-ErbB2 therapy. 相似文献109.
Oliver Kumpf Evangelos J Giamarellos-Bourboulis Alexander Koch Lutz Hamann Maria Mouktaroudi Djin-Ye Oh Eicke Latz Eva Lorenz David A Schwartz Bart Ferwerda Christina Routsi Chryssanthi Skalioti Bart-Jan Kullberg Jos WM van der Meer Peter M Schlag Mihai G Netea Kai Zacharowski Ralf R Schumann 《Critical care (London, England)》2010,14(3):1-11
Introduction
Severe sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and angiopoietin-1 (Ang-1) and -2 (Ang-2)) are mortality indicators in Malawian children with severe bacterial infection.Methods
In 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model.Results
The median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis (72%) and 82 (28%) with pneumonia, and 154 (53%) children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis (P = 0.007). Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors (6,000 versus 3,900 pg/ml, P = 0.03; and 7,700 versus 11,900 pg/ml, P = 0.02, respectively). With a logistic regression model and controlling for confounding factors, only female sex (OR, 3.95; 95% CI, 1.33 to 11.76) and low Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (P = 0.02 and 0.001, respectively).Conclusions
Lower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome. 相似文献110.
Teresa WM Fan Andrew N Lane Richard M Higashi Mohamed A Farag Hong Gao Michael Bousamra Donald M Miller 《Molecular cancer》2009,8(1):41-19