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61.
Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients 总被引:5,自引:1,他引:5
Mannucci PM; Bauer KA; Santagostino E; Faioni E; Barzegar S; Coppola R; Rosenberg RD 《Blood》1994,84(4):1314-1319
Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis. 相似文献
62.
Moderation of hemophilia A phenotype by the factor V R506Q mutation 总被引:11,自引:1,他引:11
Nichols WC; Amano K; Cacheris PM; Figueiredo MS; Michaelides K; Schwaab R; Hoyer L; Kaufman RJ; Ginsburg D 《Blood》1996,88(4):1183-1187
Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency. 相似文献
63.
José Miguel Baena-Díez Isaac Subirana Rafael Ramos Agustín Gómez de la Cámara Roberto Elosua Joan Vila Alejandro Marín-Ibáñez María Jesús Guembe Fernando Rigo María José Tormo-Díaz Conchi Moreno-Iribas Joan Josep Cabré Antonio Segura José Lapetra Miquel Quesada María José Medrano Paulino González-Diego Guillem Frontera Jaume Marrugat 《Revista espa?ola de cardiología》2018,71(4):274-282
Introduction and objectives
To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population.Methods
Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively.Results
Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women.Conclusions
All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.Full English text available from:www.revespcardiol.org/en 相似文献64.
RD Vaithilingam SH Safii NA Baharuddin LP Karen‐Ng R Saub F Ariffin H Ramli A Sharifuddin MFH Hidayat R Raman YK Chan NA Rani RA Rahim N Shahruddin SC Cheong PM Bartold RB Zain 《Oral diseases》2015,21(1):e62-e69
Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders. 相似文献
65.
66.
Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells. 相似文献
67.
Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
68.
Merino Almazán Macarena Duarte Pérez Juan Manuel Marín Pozo Juan Francisco Ortega Granados Ana Laura Muros De Fuentes Begoña Quesada Sanz Paz Gago Sánchez Ana Isabel Rodríguez Gómez Patricia Jurado García José Miguel Artime Rodríguez-Hermida Fátima Martínez Bautista María José Rueda Ramos Antonio Mora Rodríguez Beatriz Martínez Díaz María Carmen Nieto Guindo Pablo Garrido Siles Margarita Villatoro Roldán Rosa Roldán Morales José Carlos Artacho Criado Silvia María Baños Roldán Úrsula Inoriza Rueda Ángel Garrido Martínez María Teresa 《International journal of clinical pharmacy》2019,41(1):272-279
International Journal of Clinical Pharmacy - Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective... 相似文献
69.
Marroquí L Batista TM Gonzalez A Vieira E Rafacho A Colleta SJ Taboga SR Boschero AC Nadal A Carneiro EM Quesada I 《Endocrinology》2012,153(4):1663-1672
Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca2? signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling. 相似文献
70.