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991.
Nicholas B. Abt Lauren E. Miller Tara E. Mokhtari Derrick T. Lin Jeremy D. Richmon Daniel G. Deschler Mark A. Varvares Sidharth V. Puram 《American journal of otolaryngology》2021,42(6):103070
ObjectiveTo determine prognostic factors and survival patterns for different treatment modalities for nasal cavity (NC) and paranasal sinus (PS) mucosal melanoma (MM).MethodsPatients from 1973 to 2013 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and multivariable cox proportional hazard modeling were used for survival analyses.ResultsOf 928 cases of mucosal melanoma (NC = 632, PS = 302), increasing age (Hazard Ratio [HR]:1.05/year, p < 0.001), T4 tumors (HR: 1.81, p = 0.02), N1 status (HR: 6.61, p < 0.001), and PS disease (HR: 1.50, p < 0.001) were associated with worse survival. Median survival length was lower for PS versus NC (16 versus 26 months, p < 0.001). Surgery and surgery + radiation therapy (RT) improved survival over non-treatment or RT alone (p < 0.001). Adding RT to surgery did not yield a survival difference compared with surgery alone (p = 0.43). Five-year survival rates for surgery and surgery + RT were similar, at 27.7% and 25.1% (p = 0.43).ConclusionSurgery increased survival significantly over RT alone. RT following surgical resection did not improve survival. 相似文献
992.
Hannah M. Kersten Richard H. Roxburgh Nicholas Child Philip J. Polkinghorne Chris Frampton Helen V. Danesh-Meyer 《Journal of neurology》2014,261(1):37-44
A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p < 0.001)]. Macular thickness was significantly greater (p < 0.005) in five of the nine macular regions. The increase in macular thickness was due to the increased prevalence of epiretinal membranes in the myotonic dystrophy patient group (p = 0.0002): 48.2 % of myotonic dystrophy patient eyes had evidence of epiretinal membrane, compared with 12.5 % of control eyes. Examination revealed that 56.7 % of myotonic dystrophy patients had an epiretinal membrane in at least one eye. Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity. 相似文献
993.
Ahmad Samer Al-Homsi Zhongbin Lai Tara S. Roy M. Monzr Al-Malki Nicholas Kouttab Richard P. Junghans 《Transplant immunology》2014,30(1):40-45
Impairing dendritic cell (DC) function to prevent graft versus host disease (GvHD) is an appealing concept. DC antigen presentation is NF-κB pathway-dependent and bortezomib might therefore play a role in preventing alloreactivity. We obtained DC from the blood of patients enrolled in a phase I study using post-transplant cyclophosphamide and bortezomib for prevention of GvHD. Control samples were obtained from patients receiving standard GvHD prevention regimen. Pre-treatment samples were also collected from enrolled patients. DC isolated on days + 1, + 4, and + 7 showed progressive decrease in the expression of maturation markers in comparison to control. In a DC–CD4 + mixed lymphocyte reaction (MLR) where DC isolated from the recipient blood before graft infusion were the stimulator cells, T cell proliferation measured by bromodeoxyuridine (BrdU) integration was decreased in samples obtained on days + 14 and + 21 in comparison to control group. Finally, measured by real-time PCR, the expression of IκB progressively increased while the expression of NF-κB decreased in DC on days + 1, + 4, and + 7, in comparison to pre-treatment paired controls. We conclude that our data further justify exploring the role of bortezomib in GvHD prevention and propose a novel mechanism of action of bortezomib in DC. 相似文献
994.
Does Bone Resorption Stimulate Periosteal Expansion? A Cross‐Sectional Analysis of β‐C‐telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway,and Periosteal Circumference as Measured by pQCT 下载免费PDF全文
John P Kemp Adrian Sayers Lavinia Paternoster David M Evans Kevin Deere Beate St Pourcain Nicholas J Timpson Susan M Ring Mattias Lorentzon Terho Lehtimäki Joel Eriksson Mika Kähönen Olli Raitakari Marika Laaksonen Harri Sievänen Jorma Viikari Leo‐Pekka Lyytikäinen George Davey Smith William D Fraser Liesbeth Vandenput Claes Ohlsson Jon H Tobias 《Journal of bone and mineral research》2014,29(4):1015-1024
We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β‐C‐telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC). CTX and mid‐tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β = 0.19 [0.13, 0.24]) (coefficient = SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β = –0.46 [–0.52,–0.40]) and cortical thickness [β = –0.11 (–0.18, –0.03)]. CTX was positively related to bone strength as reflected by the strength‐strain index (SSI) (β = 0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single‐nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF‐κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p < 0.05 cut‐off) (n = 2379). Subsequently, we performed a meta‐analysis of associations between these SNPs and PC in ALSPAC (n = 3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n = 938), and the Young Finns Study (YFS) (n = 1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p < 0.05 cut‐off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 相似文献
995.
996.
997.
James F. Staff Richard J. Cotton Nicholas D. Warren Jackie Morton 《International archives of occupational and environmental health》2014,87(3):275-284
Purpose
To determine a reference background urinary thallium level; to compare urinary thallium data from workers to this background level; to investigate factors affecting these levels and whether creatinine correction is appropriate.Methods
Urine samples from non-occupationally exposed people (n = 273, from 113 individuals) and workers (n = 896, from 447 individuals) were analysed for thallium by ICP-MS. A reference background level was calculated, defined as the 95th percentile value of a non-occupationally exposed population. Worker data were divided into two subsets: thallium workers (those who work directly with thallium or its compounds) and general workers; and compared to the background level. Bayesian linear mixed effects modelling was used to investigate factors affecting urinary thallium concentration and the efficacy of creatinine correction for the determination of urinary thallium.Results
The reference background urinary thallium level is 0.27 μmol/mol creatinine (creatinine-corrected) or 0.40 μg/l (uncorrected). Median values were 0.11 μmol/mol creatinine or 0.17 μg/l for non-occupationally exposed people, 0.12 μmol/mol creatinine or 0.20 μg/l for general workers and 0.19 μmol/mol creatinine or 0.41 μg/l for thallium workers. Variation was lower in creatinine-corrected models. Nine per cent of samples from general workers and 39 % of samples from thallium workers exceeded the creatinine-corrected background level. By 2010, 90 % of all workers had urinary thallium levels below the 95th percentile reference background level.Conclusions
Urinary thallium concentrations were higher in thallium workers than non-occupationally exposed people and general workers. Creatinine correction is appropriate. 相似文献998.
Current methods of determining the proportion of people who benefit from a preventive intervention and the years of life gained can underestimate the former and overestimate the latter. We describe how to overcome these errors, using two examples relating to the prevention of myocardial infarction (MI) and stroke, one using a specified polypill daily from age 50 and another reducing salt intake in the population. Standard life table analysis was used to calculate the person-years of life gained without an MI or stroke, based on estimates of the incidence of these disorders in England and Wales. The proportion of individuals who benefit was taken as everyone who would, without treatment, have an MI or stroke (holistic model), rather than limiting the benefit to the proportion calculated from the relative risk reduction (reductionist model), as is current practice. Under the holistic model, 33 % of people who take the polypill from age 50 benefit, gaining, on average, 8 years of life without an MI or stroke (19 % and 14 years under the reductionist model). Estimates for reducing salt intake by 6 g/day are 33 % and 2.8 years respectively under the holistic model (6 % and 16 years under the reductionist model). In the prevention of disorders such as stroke by reducing exposure to causal factors such as blood pressure, the use of a holistic model corrects the underestimation of the proportion of people who benefit and the overestimation of their years of life gained associated with current methods. 相似文献
999.
Benjamin A. Logsdon James Y. Dai Paul L. Auer Jill M. Johnsen Santhi K. Ganesh Nicholas L. Smith James G. Wilson Russell P. Tracy Leslie A. Lange Shuo Jiao Stephen S. Rich Guillaume Lettre Christopher S. Carlson Rebecca D. Jackson Christopher J. O'Donnell Mark M. Wurfel Deborah A. Nickerson Hua Tang Alexander P. Reiner Charles Kooperberg 《Genetic epidemiology》2014,38(1):21-30
Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that “aggregate” tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare‐variant test that explicitly models a fraction of variants as neutral, tests associations at the gene‐level, and infers the rare‐variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome‐wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare‐variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans. 相似文献
1000.
Jack Goldberg Kathryn M. Magruder Christopher W. Forsberg Lewis E. Kazis T. Bedirhan Üstün Matthew J. Friedman Brett T. Litz Viola Vaccarino Patrick J. Heagerty Theresa C. Gleason Grant D. Huang Nicholas L. Smith 《Quality of life research》2014,23(5):1579-1591