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961.
uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues 总被引:10,自引:0,他引:10 下载免费PDF全文
Meng S Tripathy D Shete S Ashfaq R Saboorian H Haley B Frenkel E Euhus D Leitch M Osborne C Clifford E Perkins S Beitsch P Khan A Morrison L Herlyn D Terstappen LW Lane N Wang J Uhr J 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(46):17361-17365
Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively. 相似文献
962.
Laura A. Genovesi Ching Ging Ng Melissa J. Davis Marc Remke Michael D. Taylor David J. Adams Alistair G. Rust Jerrold M. Ward Kenneth H. Ban Nancy A. Jenkins Neal G. Copeland Brandon J. Wainwright 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(46):E4325-E4334
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964.
Jonathan N. Johnson MD FACC Cindy S. Barrett MD Wayne H. Franklin MD FACC Eric M. Graham MD FACC Nancy J. Halnon MD Brandy A. Hattendorf MD FACC Catherine D. Krawczeski MD FACC James J. McGovern MD FACC Matthew J. O'Connor MD Amy H. Schultz MD MSCE FACC Jeffrey M. Vinocur MD Devyani Chowdhury MD FACC Jeffrey B. Anderson MD MPH FACC 《Congenital heart disease》2017,12(6):756-761
965.
966.
Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis 总被引:1,自引:0,他引:1
Couthouis J Hart MP Erion R King OD Diaz Z Nakaya T Ibrahim F Kim HJ Mojsilovic-Petrovic J Panossian S Kim CE Frackelton EC Solski JA Williams KL Clay-Falcone D Elman L McCluskey L Greene R Hakonarson H Kalb RG Lee VM Trojanowski JQ Nicholson GA Blair IP Bonini NM Van Deerlin VM Mourelatos Z Shorter J Gitler AD 《Human molecular genetics》2012,21(13):2899-2911
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. Given these commonalities, we hypothesized that a related protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar properties and therefore could contribute to disease. Here, we report an analysis of EWSR1 in multiple functional assays, including mutational screening in ALS patients and controls. We identified three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals. We show that disease-specific variants affect EWSR1 localization in motor neurons. We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1. Together, our studies highlight a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease and support an emerging concept that a class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases. 相似文献
967.
Eduardo Rodríguez-Arbolí Francisco José Márquez-Malaver Nancy Rodríguez-Torres Teresa Caballero-Velázquez Virginia Escamilla-Gómez Cristina Calderón-Cabrera José Francisco Falantes-González María Solé-Rodríguez Patricia García-Ramírez María Moya-Arnao Enric Carreras Ildefonso Espigado-Tocino José Antonio Pérez-Simón 《Biology of blood and marrow transplantation》2019,25(1):183-190
Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p?=?.63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p?=?.001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p?=?.54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p?=?.83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant. 相似文献
968.
Amita Shukla-Dave Nancy Lee Hilda Stambuk Ya Wang Wei Huang Howard T Thaler Snehal G Patel Jatin P Shah Jason A Koutcher 《BMC medical physics》2009,9(1):1-9
Background
We evaluated the repeatability of the calculation of myocardial blood flow (MBF) at rest and pharmacological stress, and calculated the coronary flow reserve (CFR) utilizing 82Rb PET imaging. The aim of the research was to prove high repeatability for global MBF and CFR values and good repeatability for regional MBF and CFR values. The results will have significant impact on cardiac PET imaging in terms of making it more affordable and increasing its use.Methods
12 normal volunteers were imaged at rest and during pharmacological stress, with 2220 MBq of 82Rb each. A GE Advance PET system was used to acquire dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland). Two differential equations, describing a 2-compartmental model, were solved by numerical integration and using Levenberg-Marquardt's method for fitting data. The PMOD program defines 16 standard segments and calculates myocardial flow for each segment, as well as average septal, anterior, lateral, inferior and global flow. Repeatability was evaluated according to the method of Bland and Altman.Results
Global rest and stress MBF, as well as global CFR, showed very good repeatability. No significant differences were found between the paired resting global MBF (0.63 ± 0.13 vs. 0.64 ± 0.13 mL/min/g; mean difference, -1.0% ± 2.6%) and the stress global MBF (1.37 ± 0.23 vs. 1.37 ± 0.24; mean difference, 0.1% ± 2.3%). Global CFR was highly reproducible (2.25 ± 0.56 vs. 2.22 ± 0.54, P = not statistically significant; mean difference, 1.3% ± 14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown good reproducibility. The average per sector repeatability coefficients for rest MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average repeatability coefficient for CFR was 0.25 (10.6%).Conclusion
The results of the study show that software calculation of MBF and CFR with 82Rb myocardial PET imaging is highly repeatable for global values and has good repeatability for regional values. 相似文献969.
970.