全文获取类型
收费全文 | 684篇 |
免费 | 41篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 9篇 |
妇产科学 | 23篇 |
基础医学 | 120篇 |
口腔科学 | 2篇 |
临床医学 | 49篇 |
内科学 | 154篇 |
皮肤病学 | 5篇 |
神经病学 | 56篇 |
特种医学 | 3篇 |
外科学 | 178篇 |
综合类 | 2篇 |
预防医学 | 66篇 |
眼科学 | 6篇 |
药学 | 33篇 |
肿瘤学 | 24篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 11篇 |
2013年 | 16篇 |
2012年 | 43篇 |
2011年 | 38篇 |
2010年 | 16篇 |
2009年 | 23篇 |
2008年 | 50篇 |
2007年 | 48篇 |
2006年 | 74篇 |
2005年 | 53篇 |
2004年 | 35篇 |
2003年 | 62篇 |
2002年 | 51篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 10篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有730条查询结果,搜索用时 15 毫秒
71.
During puberty, agonistic behaviors undergo significant transitions. In golden hamsters, puberty is marked by a transition from play fighting to adult aggression. During early puberty, male golden hamsters perform play-fighting attacks. This response type is gradually replaced by adult attacks over the course of puberty. Interestingly, this behavioral transition does not appear to be controlled by changes in gonadal steroids. Instead, the shift from play fighting to adult aggression in male golden hamsters is driven by pubertal changes in glucocorticoid levels. Specifically, the transition from play fighting to adult aggression coincides with developmental increases in glucocorticoid levels, and external manipulations such as social stress or treatment with corticosteroid receptor agonists accelerate this behavioral shift. Moreover, the consequences of social stress differ greatly between juvenile and adult male golden hamsters. Although a single defeat during adulthood causes severe and long lasting behavioral and neuroendocrine consequences, socially subjugated juveniles show only transient behavioral effects. As such, it is likely that pubertal changes in the HPA axis are not only linked to the maturation of offensive responses but also determine the consequences of social stress. Combined, these studies in golden hamsters provide a novel mechanism for the development of agonistic behavior and suggest that age related differences in behavioral plasticity are mediated by the development of the HPA axis. 相似文献
72.
73.
Choukroun G Deray G Glotz D Lebranchu Y Dussol B Bourbigot B Lefrançois N Cassuto-Viguier E Toupance O Hacen C Lang P Mazouz H Martinez F 《Néphrologie & thérapeutique》2008,4(7):575-583
The management of anemia after kidney transplantation remains poorly explored. The Management of Anemia in French Kidney Transplant Patients (MATRIX) study is an observational study conducted in 10 academic hospitals among kidney-transplant patients designed to evaluate the prevalence, associated factors and management of post-transplant anemia. Over two consecutive weeks, 418 recipients (males: 248; age: 50.8+/-12.7 years) were included, all were transplanted for more than six months. Mean serum creatinine (Scr) was 152+/-67 micromol/l and mean hemoglobin (Hb) was 12.4+/-1.8 g/dl (males: 12.8+/-1.9 g/dl; females 11.9+/-1.6 g/dl). Irrespective of the delay following transplantation, 23% of patients (n=95) were severely anemic (Hb < or = 11 g/dl). Eighteen percent of the patients received an antianemic treatment (10% oral iron, 7% erythropoiesis stimulating agents (ESA), 4% folic acid) and only 35% of the severely anemic patients were actually treated (n=33). A significantly-negative correlation was observed between eGFR and Hb levels (R= -0.347, p<0.02). Ninety-six percent of the 193 patients transplanted for more than six months and a Scr greater than 150 micromol/l (n=185) suffered at least one comorbidity (89% hypertension, 32% hypercholesterolemia, 13% diabetes); this group represent the second cohort. Seventy-four percent of them were treated with mycophenolate mofetil, 16% with azathioprine, and 62% with an ACEI or angiotensin II receptor antagonists. Since the transplantation, 127 patients (66%) have been anemic (Hb < or = 11 g/dl) and 58% (n=112) were treated (iron and/or ESA, respectively 81 and 55%). Among the patients not treated for anemia, 74% had an Hb level below 12g/dl. ESA-treated patients received a mean dose of 8500 UI+/-2800 per week. Anemia is under-diagnosed and under-treated in renal-transplant recipients, despite its high prevalence. As expected, a correlation between renal function and Hb levels was observed, as in CKD patients. Prospective studies are underway to assess the consequences of postkidney transplant anemia on quality of life, cardiovascular morbidity and chronic allograft nephropathy and to define the benefit of the treatment. 相似文献
74.
Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for Hodgkin's disease 总被引:5,自引:0,他引:5
Cryopreservation of ovarian tissue is now offered as an experimental procedure to preserve the fertility of young patients with a high risk for premature ovarian failure resulting from cancer therapy. This is the only available option to preserve the fertility of prepubertal patients treated with gonadotoxic chemotherapy. At present, thousands of patients all over the world have undergone this procedure with the hope of later restoring their fertility. Although the efficiency of the transplantation of cryopreserved ovarian tissue to restore ovarian function has been established, reports of pregnancy are still very scarce. Here, we describe the second published full-term spontaneous pregnancy after an orthotopic and heterotopic transplantation of cryopreserved ovarian tissue in a 31-year-old woman previously treated by conditioning therapy for bone marrow transplantation for Hodgkin's disease. This birth gives compelling evidence for the graft origin of the gamete and confirms the efficacy of ovarian tissue transplantation in restoring human natural fertility after oncological treatment. This case report stresses the importance of proposing the ovarian tissue cryopreservation procedure to all young patients who require potentially sterilizing treatment, with all alternative options to preserve fertility being duly taken into consideration. 相似文献
75.
76.
Sandrine Cappellesso Jean-Fran?ois Valentin Bruno Giraudeau Marie-Denise Boulanger Azmi Al-Najjar Mathias Büchler Jean-Michel Halimi Hubert Nivet Pierre Bardos Yvon Lebranchu Hervé Watier 《Nephrology, dialysis, transplantation》2004,19(2):439-443
BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes. 相似文献
77.
Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro 总被引:12,自引:0,他引:12
Hanouz JL Yvon A Massetti M Lepage O Babatasi G Khayat A Bricard H Gérard JL 《Anesthesiology》2002,97(1):33-41
BACKGROUND: The authors examined the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels, adenosine A1 receptor, and alpha and beta adrenoceptors in desflurane-induced preconditioning in human myocardium, in vitro. METHODS: The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34 degrees C; stimulation frequency, 1 Hz). Before a 30-min anoxic period, 3, 6, and 9% desflurane was administered during 15 min. Desflurane, 6%, was also administered in the presence of 10 microm glibenclamide, a K(ATP) channels antagonist; 10 microm HMR 1098, a sarcolemmal K(ATP) channel antagonist; 800 microm 5-hydroxy-decanoate (5-HD), a mitochondrial K(ATP) channel antagonist; 1 microm phentolamine, an alpha-adrenoceptor antagonist; 1 microm propranolol, a beta-adrenoceptor antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine (DPX), the adenosine A1 receptor antagonist. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). RESULTS: Desflurane at 3% (95 +/- 13% of baseline), 6% (86 +/- 6% of baseline), and 9% (82 +/- 6% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (50 +/- 11% of baseline). Glibenclamide (60 +/- 12% of baseline), 5-HD (57 +/- 21% of baseline), DPX (63 +/- 19% of baseline), phentolamine (56 +/- 20% of baseline), and propranolol (63 +/- 13% of baseline) abolished desflurane-induced preconditioning. In contrast, HMR 1098 (85 +/- 12% of baseline) did not modify desflurane-induced preconditioning. CONCLUSIONS: In vitro, desflurane preconditions human myocardium against simulated ischemia through activation of mitochondrial K(ATP) channels, adenosine A1 receptor, and alpha and beta adrenoceptors. 相似文献
78.
Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection 总被引:6,自引:0,他引:6
Dharancy S Malapel M Perlemuter G Roskams T Cheng Y Dubuquoy L Podevin P Conti F Canva V Philippe D Gambiez L Mathurin P Paris JC Schoonjans K Calmus Y Pol S Auwerx J Desreumaux P 《Gastroenterology》2005,128(2):334-342
BACKGROUND AND AIMS: Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity. METHODS: PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA).The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid. RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls. CONCLUSIONS: HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury. 相似文献
79.
Zompi S Tulliez M Conti F Leblond V Gaulard P Blanche P Durand F Ghandi D Dreyfus F Louvel A Calmus Y Bouscary D 《Journal of hepatology》2000,32(3):521-527
BACKGROUND/AIMS: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. METHODS: Rituximab (IDEC-C2HB8; Roche Laboratories, Neuilly-sur-Seine, France) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS: The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION: These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders. 相似文献
80.
Overexpression of the Notch ligand,Jagged-1, induces alloantigen-specific human regulatory T cells 总被引:14,自引:1,他引:14
Yvon ES Vigouroux S Rousseau RF Biagi E Amrolia P Dotti G Wagner HJ Brenner MK 《Blood》2003,102(10):3815-3821
Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic hematopoietic stem cell transplantation. Techniques to prevent GVHD have included ex vivo T-cell depletion of the graft or prolonged in vivo immunosuppression. Both reduce the frequency and severity of GVHD but also reduce T-cell-mediated graft-versus-malignancy effect, and increase the risk of infection. A major goal in transplantation is to prevent alloreactivity while preserving activity against tumors and infectious agents. We have used activation of the Notch pathway to try to generate T cells able to specifically regulate alloantigen responses. We used allogeneic Epstein-Barr virus lymphoblastoid B cells (EBV-LCLs) as stimulator cells. Such LCLs are excellent (allo) antigen-presenting cells and can be obtained in large numbers even from donors who have received extensive chemo/radiotherapy. We overexpressed a Notch ligand, Jagged-1, in these cells by adenoviral vector transduction. Stimulation of CD45RA+ naive T cells by Jagged-1 EBV-LCL reduces production of interferon-gamma, interleukin-2, and interleukin-5, but up-regulates transforming growth factor-beta 1 synthesis, consistent with induction of a regulatory T-cell phenotype. Transfer of these T cells to fresh lymphocyte cultures inhibits proliferative and cytotoxic immune responses to the priming alloantigens while sparing responses to third-party stimulator cells. Notch activation in the presence of alloantigen-presenting cells may therefore be a means of inducing specific regulatory T cells while preserving other T-cell functionality. 相似文献