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31.
Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study 总被引:2,自引:0,他引:2
Asnafi V Buzyn A Thomas X Huguet F Vey N Boiron JM Reman O Cayuela JM Lheritier V Vernant JP Fiere D Macintyre E Dombret H 《Blood》2005,105(8):3072-3078
Patients with T-cell acute lymphoblastic leukemias (T-ALLs) within the Leucemies Aigues Lymphoblastiques de l'Adulte-94 (LALA-94) prospective trial were treated with a 4-drug per 4-week induction, with intermediate-dose cytarabine and mitoxantrone salvage treatment for patients not achieving complete remission (CR) in 1 course. Only the latter received allografts, if possible, thus providing an informative setting for assessing early response. Representative patients with T-ALL (91 patients) were classified into surface T-cell receptor (TCR)-expressing T-ALL patients (TCRalphabeta+ or TCRgammadelta+), pre-alphabeta T-ALL patients (cTCRbeta+, TCR-), and immature (IM) cTCRbeta-, TCR- T-ALL patients; 81 patients underwent genotyping for SIL-TAL1, CALM-AF10, HOX11, and HOX11L2. Overall, CR was obtained in 81 (89%) patients; relapse rate was 62% at 4 years and overall survival (OS) rate was 38%. CR rate was significantly lower in IM T-ALL patients after 1 course (45% vs 87%; P < .001) and after salvage (74% vs 97%; P = .002), with the latter inducing a higher rate of CR (9 [64%] of 14) than initial induction. Once CR was obtained, cumulative relapse rates were similar for IM, pre-alphabeta, and TCR+ T-ALL patients (P = .51), but were higher in HOX11L2 (83%) and SIL-TAL1 (82%) T-ALL patients compared with other genetic subgroups (48%; P = .05). This was associated with an inferior OS for HOX11L2 T-ALLs (13% vs 47% in HOX11L2-T-ALLs; P = .009). The majority of patients with HOX11 T-ALL underwent allografting, predominantly in second CR, but were not associated with a superior OS. Both TCR and genotypic stratification can therefore contribute to risk-adapted management of adult T-ALLs. 相似文献
32.
Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase
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Gardembas M Rousselot P Tulliez M Vigier M Buzyn A Rigal-Huguet F Legros L Michallet M Berthou C Cheron N Maloisel F Mahon FX Facon T Berthaud P Guilhot J Guilhot F;CML French Group 《Blood》2003,102(13):4298-4305
In chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response. 相似文献
33.
Requirement for mitogen-activated protein kinase activation in the response of embryonic stem cell-derived hematopoietic cells to thrombopoietin in vitro 总被引:1,自引:2,他引:1
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Filippi MD Porteu F Le Pesteur F Schiavon V Millot GA Vainchenker W de Sauvage FJ Dubart Kupperschmitt A Sainteny F 《Blood》2002,99(4):1174-1182
Enforced expression of c-mpl in embryonic stem (ES) cells inactivated for this gene results in protein expression in all the ES cell progeny, producing cells that do not belong to the megakaryocytic lineage and are responsive to PEG-rhuMGDF, a truncated form of human thrombopoietin (TPO) conjugated to polyethylene glycol. These include a primitive cell called BL-CFC, thought to represent the equivalent of the hemangioblast, and all myeloid progenitor cells. In this model, PEG-rhuMGDF was able to potentiate the stimulating effects of other growth factors, including vascular endothelial growth factor, on BL-CFC and a combination of cytokines on the growth of granulocyte macrophage-colony-forming units. The importance of the C-terminal domain of Mpl and of mitogen-activated protein kinase (MAPK) activation in TPO-dependent megakaryocytic differentiation has been well studied in vitro. Here, the role of this domain and the involvement of MAPK in upstream and nonmegakaryocytic cells are examined by using 2 truncated mutants of Mpl (Delta34, deletion of residues 71 to 121 in the C-terminal domain; and Delta3, deletion of residues 71-94) and specific inhibitors of the MAPK pathway. The 2 deleted regions support different functions, mediated by different signals. Residues 71 to 121 were required for PEG-rhuMGDF-dependent growth of BL-CFC, for megakaryocytic and other myeloid progenitors, and for megakaryocyte polyploidization. These responses were mediated by the ERK1-ERK2 MAPK pathway. In contrast, the only function of the sequence comprising residues 71 to 94 was to mediate the synergistic effects of PEG-rhuMGDF with other hematopoietic growth factors. This function is not mediated by MAPK activation. 相似文献
34.
Association between leptin, metabolic factors and liver histology in patients with chronic hepatitis C. 总被引:3,自引:0,他引:3
Robert P Myers Djamila Messous Thierry Poynard Francoise Imbert-Bismut 《Journal canadien de gastroenterologie》2007,21(5):289-294
BACKGROUND: Steatosis is common in hepatitis C virus (HCV)-infected patients and likely accelerates fibrosis progression. Leptin, the peptide product of the obesity gene (ob), has been implicated in hepatic fibrogenesis; circulating levels of leptin correlate with body fat mass. The objective of the present study was to determine the clinical and histological correlates of serum leptin in HCV-infected patients, and to determine its utility in predicting liver histological lesions. PATIENTS AND METHODS: In 62 patients with chronic HCV, serum leptin was measured using a commercially available immunoassay. Associations between leptin, metabolic parameters, and severe hepatic fibrosis (stages 2 to 4) and steatosis (30% or greater) were determined. The utility of leptin in predicting liver histology was determined using receiver operating characteristic (ROC) curves. RESULTS: The median body mass index (BMI) was 23.2 kg/m2 (range 17.7 kg/m2 to 35.6 kg/m2); 16% of patients (n=10) had HCV genotype 3. Severe fibrosis and steatosis were present in 23% and 13% of patients, respectively. Leptin was strongly correlated with the BMI, and its levels were higher in women. BMI-corrected leptin levels were not independently associated with severe fibrosis but were significantly associated with steatosis (OR of 1.07; 95% CI 1.01 to 1.04). On it own, leptin was poorly predictive of severe steatosis (area under the ROC curve was 0.64; 95% CI 0.42 to 0.87). However, its accuracy improved with the addition of HCV genotype (area under the ROC curve was 0.86; 95% CI 0.72 to 1.00; P=0.07). CONCLUSIONS: As observed in the non-HCV setting, serum leptin correlates with BMI; higher leptin levels are found in women than men with chronic HCV. Serum leptin is a poor predictor of HCV-related fibrosis but may play a role in predicting steatosis when combined with HCV genotype. 相似文献
35.
Simon Giroux Jinwang Xu T. Jagadeeswar Reddy Mark Morris KevinM. Cottrell Caroline Cadilhac James A. Henderson Oliver Nicolas Darius Bilimoria Francois Denis Nagraj Mani Nigel Ewing Rebecca Shawgo Lucille L’Heureux Subajini Selliah Laval Chan Nathalie Chauret Francoise Berlioz-Seux Mark N. Namchuk Anne-Laure Grillot Youssef L. Bennani Sanjoy K. Das John P. Maxwell 《ACS medicinal chemistry letters》2014,5(3):240-243
36.
John Routes Mario Abinun Waleed Al-Herz Jacinta Bustamante Antonio Condino-Neto Maria Teresa De La Morena Amos Etzioni Eleonora Gambineri Elie Haddad Lisa Kobrynski Francoise Le Deist Shigeaki Nonoyama Joao Bosco Oliveira Elena Perez Capucine Picard Nima Rezaei John Sleasman Kathleen E. Sullivan Troy Torgerson 《Journal of clinical immunology》2014,34(4):398-424
Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies. 相似文献
37.
Maternal complex chromosomal rearrangement leads to TCF12 microdeletion in a patient presenting with coronal craniosynostosis and intellectual disability
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38.
Christophe Bologna Leila Edno Juan-Manuel Anaya Francois Canovas Marc Vanden Berghe Christian Jorgensen Marc Galtier Bernard Combe Francoise Bressolle Jacques Sany 《Arthritis \u0026amp; Rheumatology》1994,37(12):1770-1773
Objective. To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients. Methods. Ten RA patients (9 women, 1 man; mean ± SD age 49.2 ± 10.6, mean disease duration 13.2 ± 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean ± SD MTX treatment duration was 26.4 ± 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean ± SD of 19.7 ± 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues. Results. The mean ± SD plasma concentration was 0.0252 ± 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 ± 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 ± 0.164 and 0.286 ± 0.126 nmoles/gm, respectively. Conclusion. After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients. 相似文献
39.
40.
De Kermadec Heloïse Bequignon Emilie Zerah-Lancner Francoise Garin Antoine Devars du Mayne Marie Coste André Louis Bruno Papon Jean-François 《European archives of oto-rhino-laryngology》2019,276(5):1391-1396
European Archives of Oto-Rhino-Laryngology - Stress has been suspected to play a role in rhinitis. The role of stress on nasal patency has been not yet elucidated. The aim was to evaluate the... 相似文献