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991.
Tester DJ Kopplin LJ Creighton W Burke AP Ackerman MJ 《Mayo Clinic proceedings. Mayo Clinic》2005,80(5):596-600
OBJECTIVE: To perform a molecular autopsy involving the RyR2-encoded cardiac ryanodine receptor/calcium release channel to determine whether mutations responsible for catecholaminergic polymorphic ventricular tachycardia (CPVT) represent a novel pathogenic basis for unexplained drownings. METHODS: A cardiac channel molecular autopsy was performed on 2 individuals who died of unexplained drowning and whose cases were referred to the Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn. Comprehensive mutational analysis of all 60 protein-encoded exons of the 5 long QT syndrome-causing cardiac channel genes and a targeted analysis of 18 RyR2 exons known to host RyR2-mediated CPVT-causing mutations (CPVT1) was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. RESULTS: Both individuals harbored novel mutations in RyR2. Postmortem mutational analysis revealed a familial missense mutation in exon 14, R414C, in a 16-year-old girl. A 9-year-old boy possessed a sporadic missense mutation in exon 49, V2475F. Both amino acid positions involve highly conserved residues that localize to critical functional domains in the calcium release channel. Neither substitution was present in 1000 reference alleles. CONCLUSIONS: This molecular autopsy study provides proof of principle that RyR2 mutations can underlie some unexplained drownings. A population-based genetic epidemiology study that involves molecular autopsies of individuals who die of unexplained drowning is needed to determine the prevalence and spectrum of KCNQ1 and now RyR2 mutations as potential pathogenic mechanisms for drowning. 相似文献
992.
Jingmei Hsu Andrew Artz Sebastian A. Mayer Danielle Guarner Michael R. Bishop Ronit Reich-Slotky Sonali M. Smith June Greenberg Justin Kline Rosanna Ferrante Adrienne A. Phillips Usama Gergis Hongtao Liu Wendy Stock Melissa Cushing Tsiporah B. Shore Koen van Besien 《Biology of blood and marrow transplantation》2018,24(2):359-365
Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n?=?9, 21%), CLL (n?=?5, 12%) and non-Hodgkin lymphomas (n?=?28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival, progression-free survival, and overall survival were 53%, 62%, and 65%, respectively, for these patients. Only 8% of the survivors had chronic GVHD. In conclusion, haplo-cord transplantation offers a transplant alternative for patients with recurrent or refractory lymphoid malignancies who lack matching donors. Both neutrophil and platelet count recovery is rapid, nonrelapse mortality is limited, excellent disease control can be achieved, and the incidence of chronic GVHD is limited. Thus, haplo-cord achieves high rates of engraftment and encouraging results. 相似文献
993.
Greco NJ Lee WR Kurtz J Seetharaman S Moroff G 《Journal of hematotherapy & stem cell research》2003,12(2):199-213
Unlike granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, which show a single homogeneous population of CD34(+) cells, umbilical cord blood (CB) CD34(+) cells are present as multiple populations, CD34(regular) and CD34(bright) (the latter comprising 7.0-58.2% of the total CD34(+) cells), using the ProCOUNT trade mark procedure or with anti-CD34 labeling of immunoselected cells. The CD34(regular) population contains cells with high forward scatter (CD34(regular)FSC(high)) and with low forward scatter (CD34(regular) FSC(low)). Immunomagnetically selected CD34(+) cells, sorted into CD34(regular), CD34(regular) FSC(high), CD34(regular)FSC(low), and CD34(bright) cell populations, were used in in vitro assays: only the CD34(regular)FSC(high) population transmigrated and showed growth of colony-forming unit (CFU) and long-term culture initiating cells (LTC-IC) colonies. The absolute number of CD34(+) cells in CB samples was determined by ProCOUNT trade mark and Stem Kit trade mark enumeration protocols. In liquid stored CB units, ProCOUNT trade mark and Stem Kit trade mark count differences are accounted for by the enumeration of CD34(bright) cells. Differences between ProCOUNT trade mark and Stem Kit trade mark counts using cryopreserved/thawed samples are accounted for by increased CD34(regular) FSC(low) cell numbers (2.0 +/- 1.4% in liquid stored and 27.8 +/- 14.6% in cryopreserved/thawed samples). The ProCOUNT trade mark assay includes the nonfunctional CD34(bright) and CD34(regular)FSC(low) cells as part of the CD34(+) cell count, thereby elevating the absolute number of CD34(+) cells. Using the Stem Kit trade mark assay method of gating, CD34(bright) and CD34(regular)FSC(low) cells are not counted. Our data indicate that the CD34(regular)FSC(high) cell population has functional characteristics based on the in vitro assays and a more accurate count of these cells can be achieved using the Stem Kit trade mark assay. 相似文献
994.
Reid W 《Professional nurse (London, England)》2002,17(12):734-737
The development of a draft guideline on confirming placement of nasogastric tubes laid the basis for a senior nurse to use the principles of clinical governance to lead an improvement in practice. Key factors included risk management, dissemination of draft guidelines reflecting current evidence and changing practice. Good communication was vital to the project. 相似文献
995.
Linshan Shang Lindsay B. Henderson Megan T. Cho Donald S. Petrey Chin-To Fong Katrina M. Haude Natasha Shur Julie Lundberg Natalie Hauser Jason Carmichael Jeffrey Innis Jane Schuette Yvonne W. Wu Shailesh Asaikar Margaret Pearson Leandra Folk Kyle Retterer Kristin G. Monaghan Wendy K. Chung 《Neurogenetics》2016,17(1):43-49
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