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991.
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Man S Rahmattulla C Maan AC Holman E Bax JJ van der Wall EE Schalij MJ Swenne CA 《Journal of electrocardiology》2012,45(2):154-160
IntroductionCurrent criteria for electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH) have a low diagnostic accuracy. Addition of demographic, anthropomorphic, and additional ECG variables may improve accuracy. As hypertrophy affects action potential morphology and intraventricular conduction, QRS prolongation and T-wave morphology may occur and become manifest in the vectorcardiographic variables spatial QRS-T angle (SA) and spatial ventricular gradient. In this study, we attempted to improve the diagnostic accuracy for LVH by using a combination of demographic, anthropomorphic, ECG, and vectorcardiographic variables.MethodsThe study group (n = 196) was divided in 4 subgroups with, on one hand, echocardiographically diagnosed LVH or a normal echocardiogram and, on the other hand, with any of the conventional ECG signs for LVH or with normal ECGs. Each subgroup was randomly split into halves, yielding 2 equally-sized (n = 98) data sets A and B. Age, sex, height, weight, body mass index, body surface area (BSA), frontal QRS axis, QRS duration, QT duration, maximal QRS vector magnitude, SA, and ventricular gradient magnitude and orientation were univariate studied by receiver operating characteristic analysis and were used to build a stepwise linear discriminant model using P < .05 as entry and P > .10 as removal criterion. The discriminant model was built in set A (model A) and tested on set B. Stability checks were done by building a discriminant model on set B and testing on set A and by cross-validation analysis in the complete study group.ResultsThe discriminant model equation was D = 5.130 × BSA ? 0.014 × SA ? 8.74, wherein D greater than or equal to 0 predicts a normal echocardiogram and D less than 0 predicts LVH. The diagnostic accuracy (79%) was better than the diagnostic accuracy of conventional ECG criteria for LVH (57%).ConclusionThe combination of BSA and SA yields a diagnostic accuracy of LVH that is superior to that of the conventional ECG criteria. 相似文献
993.
Huillard E Hashizume R Phillips JJ Griveau A Ihrie RA Aoki Y Nicolaides T Perry A Waldman T McMahon M Weiss WA Petritsch C James CD Rowitch DH 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(22):8710-8715
Although malignant astrocytomas are a leading cause of cancer-related death in children, rational therapeutic strategies are lacking. We previously identified activating mutations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) (BRAF(T1799A) encoding BRAF(V600E)) in association with homozygous cyclin-dependent kinase inhibitor 2A (CDKN2A, encoding p14ARF and p16Ink4a) deletions in pediatric infiltrative astrocytomas. Here we report that BRAF(V600E) expression in neural progenitors (NPs) is insufficient for tumorigenesis and increases NP cellular differentiation as well as apoptosis. In contrast, astrocytomas are readily generated from NPs with additional Ink4a-Arf deletion. The BRAF(V600E) inhibitor PLX4720 significantly increased survival of mice after intracranial transplant of genetically relevant murine or human astrocytoma cells. Moreover, combination therapy using PLX4720 plus the Cyclin-dependent kinase (CDK) 4/6-specific inhibitor PD0332991 further extended survival relative to either monotherapy. Our findings indicate a rational therapeutic strategy for treating a subset of pediatric astrocytomas with BRAF(V600E) mutation and CDKN2A deficiency. 相似文献
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Orna Staretz-Chacham Iris Noyman Ohad Wormser Abed Abu Quider Guy Hazan Iris Morag Noam Hadar Kimiyo Raymond Ohad S. Birk Carlos R. Ferreira Arie Koifman 《Clinical genetics》2020,97(6):920-926
A congenital disorder of glycosylation due to biallelic mutations in B4GALT1 has been previously reported in only three patients with two different mutations. Through homozygosity mapping followed by segregation analysis in an extended pedigree, we identified three additional patients homozygous for a novel mutation in B4GALT1, expanding the phenotypic spectrum of the disease. The patients showed a uniform clinical presentation with intellectual disability, marked pancytopenia requiring chronic management, and novel features including pulmonary hypertension and nephrotic syndrome. Notably, affected individuals exhibited a moderate elevation of Man3GlcNAc4Fuc1 on serum N-glycan analysis, yet two of the patients had a normal pattern of transferrin glycosylation in repeated analysis. The novel mutation is the third disease-causing variant described in B4GALT1, and the first one within its transmembrane domain. 相似文献
997.
David N. Louis Pieter Wesseling Kenneth Aldape Daniel J. Brat David Capper Ian A. Cree Charles Eberhart Dominique Figarella‐Branger Maryam Fouladi Gregory N. Fuller Caterina Giannini Christine Haberler Cynthia Hawkins Takashi Komori Johan M. Kros HK Ng Brent A. Orr Sung‐Hye Park Werner Paulus Arie Perry Torsten Pietsch Guido Reifenberger Marc Rosenblum Brian Rous Felix Sahm Chitra Sarkar David A. Solomon Uri Tabori Martin J. van den Bent Andreas von Deimling Michael Weller Valerie A. White David W. Ellison 《Brain pathology (Zurich, Switzerland)》2020,30(4):844-856
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles—relating to classification categories, approaches to classification, nomenclature, and grading—that the group hopes will also inform the future classification of CNS neoplasms. 相似文献
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Andrea Cerase Daniel Smeets Y. Amy Tang Michal Gdula Felix Kraus Mikhail Spivakov Benoit Moindrot Marion Leleu Anna Tattermusch Justin Demmerle Tatyana B. Nesterova Catherine Green Arie P. Otte Lothar Schermelleh Neil Brockdorff 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(6):2235-2240