全文获取类型
收费全文 | 544篇 |
免费 | 71篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 6篇 |
妇产科学 | 8篇 |
基础医学 | 48篇 |
口腔科学 | 4篇 |
临床医学 | 43篇 |
内科学 | 163篇 |
皮肤病学 | 112篇 |
神经病学 | 51篇 |
特种医学 | 10篇 |
外科学 | 115篇 |
预防医学 | 27篇 |
眼科学 | 3篇 |
药学 | 6篇 |
肿瘤学 | 18篇 |
出版年
2022年 | 8篇 |
2021年 | 11篇 |
2020年 | 14篇 |
2019年 | 29篇 |
2018年 | 29篇 |
2017年 | 17篇 |
2016年 | 21篇 |
2015年 | 15篇 |
2014年 | 23篇 |
2013年 | 28篇 |
2012年 | 38篇 |
2011年 | 31篇 |
2010年 | 15篇 |
2009年 | 24篇 |
2008年 | 43篇 |
2007年 | 27篇 |
2006年 | 32篇 |
2005年 | 16篇 |
2004年 | 21篇 |
2003年 | 17篇 |
2002年 | 23篇 |
2001年 | 17篇 |
2000年 | 15篇 |
1999年 | 18篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 12篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 8篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有616条查询结果,搜索用时 31 毫秒
11.
San Miguel JF Lahuerta JJ García-Sanz R Alegre A Bladé J Martinez R García-Laraña J De La Rubia J Sureda A Vidal MJ Escudero A Pérez-Esquiza E Conde E García-Ruiz JC Cabrera R Caballero D Moraleda JM Leon A Besalduch J Hernandez MT Rifon J Hernandez F Solano C Palomera L Parody R Gonzalez JD Mataix R Maldonado J Constela J Carrera D Bello JL De Pablos JM Pérez-Simón JA Torres JP Olanguren J Prieto E Acebede G Peñarrubia MJ Torres P Díez-Martín JL Rivas A Sánchez JM Díaz-Mediavilla J 《The hematology journal : the official journal of the European Haematology Association / EHA》2000,1(1):28-36
12.
Brenno Astiarraga Valéria B. Chueire Aglécio L. Souza Ricardo Pereira-Moreira Sarah Monte Alegre Andrea Natali Andrea Tura Andrea Mari Ele Ferrannini Elza Muscelli 《Diabetologia》2018,61(8):1829-1837
Aims/hypothesis
Incretin effect—the potentiation of glucose-stimulated insulin release induced by the oral vs the i.v. route—is impaired in dysglycaemic states. Despite evidence from human islet studies that NEFA interfere with incretin function, little information is available about the effect in humans. We tested the impact of acute bidirectional NEFA manipulation on the incretin effect in humans.Methods
Thirteen individuals with type 2 diabetes and ten non-diabetic volunteers had a 3 h OGTT, and, a week later, an i.v. isoglycaemic glucose infusion (ISO; OGTT matched). Both pairs of studies were repeated during an exogenous lipid infusion in the non-diabetic volunteers, and following acipimox administration (to inhibit lipolysis) in people with diabetes. Mathematical modelling of insulin secretion dynamics assessed total insulin secretion (TIS), beta cell glucose sensitivity (β-GS), glucose-induced potentiation (PGLU) and incretin-induced potentiation (PINCR); the oral glucose sensitivity index was used to estimate insulin sensitivity.Results
Lipid infusion increased TIS (from 61 [interquartile range 26] to 78 [31] nmol/m2 on OGTT and from 29 nmol/m2 [26] to 57 nmol/m2 [30] on ISO) and induced insulin resistance. PINCR decreased from 1.6 [1.1] to 1.3 [0.1] (p?<?0.05). β-GS, PGLU and glucagon, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses were unaffected. Acipimox (lowering NEFA by ~55%) reduced plasma glucose and TIS and enhanced insulin sensitivity, but did not change β-GS, PINCR, PGLU or glucagon, GLP-1 or GIP responses. As the per cent difference, incretin effect was decreased in non-diabetic participants and unchanged in those with diabetes.Conclusions/interpretation
Raising NEFA selectively impairs incretin effect and insulin sensitivity in non-diabetic individuals, while acute NEFA reduction lowers plasma glucose and enhances insulin sensitivity in people with diabetes but does not correct the impaired incretin-induced potentiation.13.
14.
Dr. Maria-Luisa Alegre MD PhD Deborah J. Lenschow Jeffrey A. Bluestone PhD 《Digestive diseases and sciences》1995,40(1):58-64
The main objective of our studies has been to optimize the effects of monoclonal antibodies (MAbs) and other immunosuppressive reagents to enhance organ graft survival. One such agent is OKT3, a MAb that is directed against the CD3 component of the human T-cell receptor (TCR) complex. Treatment of a rejection episode with OKT3 results in a rapid and efficient clearing of circulating T cells and reversal of most rejection episodes. Its wider use in transplantation and in the treatment of immune-mediated disease is limited by adverse reactions that follow the initial dose, the production of neutralizing Abs, and the transient nature of the immunosuppression. We have engineered CDR-grafted humanized anti-CD3 MAbs that lack Fc-receptor binding activity through mutagenesis of amino acids in the Fc portion of the MAb. This results in an immunosuppressive anti-CD3 MAb that is less antigenic and one that does not induce the first-dose side effects. In addition, we have pursued a goal of developing a therapy that will induce donor-specific tolerance while maintaining overall recipient immune competency. Because antigen-specific T-cell activation depends not only on TCR-ligand interaction, but also on additional costimulatory signals mediated by accessory molecules such as CD28, blocking the binding of CD28 on T cells to its ligand B7, during TCR engagement, might modulate transplantation responses. Using a soluble fusion protein of human CTLA4, CTLA4-Ig, that binds B7 with high affinity, inhibition of human pancreatic islet rejection that occurs, at least in part, by affecting T-cell recognition of human B7+ antigen-presenting cells has been demonstrated. In addition, CTLA4-Ig induces long-term, donor-specific unresponsiveness. 相似文献
15.
Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma 总被引:1,自引:0,他引:1
A. Alegre M. Lamana R. Arranz M. J. Fernández-Villalta J. F. Tomás A. Figuera R. Cámara J. L. Steegman F. Casado M. J. Requena J. L. Planas L. Vazquez A. Granda J. M. Fernández-Rañada 《British journal of haematology》1995,91(2):380-386
Summary. Twenty-four patients with multiple myeloma (MM), three (12-5%) in complete remission (CR) and 21 (87-5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg-l-melphalan 140mg/m2 ) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy) + rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan + melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival. 相似文献
16.
Christopher P. Montgomery Melvin Daniels Fan Zhao Maria-Luisa Alegre Anita S. Chong Robert S. Daum 《Infection and immunity》2014,82(5):2125-2134
Although many microbial infections elicit an adaptive immune response that can protect against reinfection, it is generally thought that Staphylococcus aureus infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent infection, in which S. aureus skin and soft tissue infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-γ) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-γ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI. 相似文献
17.
Carlos Jiménez-Romero Oscar Caso Maestro Félix Cambra Molero Iago Justo Alonso Cristina Alegre Torrado Alejandro Manrique Municio Jorge Calvo Pulido Carmelo Loinaz Segurola Enrique Moreno González 《World journal of gastroenterology : WJG》2014,20(31):10691-10702
The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. 相似文献
18.
Paiva B Gutiérrez NC Rosiñol L Vídriales MB Montalbán MÁ Martínez-López J Mateos MV Cibeira MT Cordón L Oriol A Terol MJ Echeveste MA de Paz R de Arriba F Palomera L de la Rubia J Díaz-Mediavilla J Sureda A Gorosquieta A Alegre A Martin A Hernández MT Lahuerta JJ Bladé J San Miguel JF;PETHEMA/GEM 《Blood》2012,119(3):687-691
The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated. 相似文献
19.
Rosiñol L García-Sanz R Lahuerta JJ Hernández-García M Granell M de la Rubia J Oriol A Hernández-Ruiz B Rayón C Navarro I García-Ruiz JC Besalduch J Gardella S López Jiménez J Díaz-Mediavilla J Alegre A San Miguel J Bladé J;PETHEMA/Spanish Myeloma Group 《Haematologica》2012,97(4):616-621