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排序方式: 共有209条查询结果,搜索用时 703 毫秒
31.
Boige V Taïeb J Hebbar M Malka D Debaere T Hannoun L Magherini E Mignard D Poynard T Ducreux M 《European journal of cancer (Oxford, England : 1990)》2006,42(4):456-459
This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC. 相似文献
32.
Jeong LS Lee HW Jacobson KA Kim HO Shin DH Lee JA Gao ZG Lu C Duong HT Gunaga P Lee SK Jin DZ Chun MW Moon HR 《Journal of medicinal chemistry》2006,49(1):273-281
We have established structure-activity relationships of novel 4'-thionucleoside analogues as the A(3) adenosine receptor (AR) agonists. Binding affinity, selectivity toward other AR subtypes, and efficacy in inhibition of adenylate cyclase were studied. From this study, 2-chloro-N(6)-methyl-4'-thioadenosine-5'-methyluronamide (36a) emerged as the most potent and selective agonist at the human A(3) AR. We have also revealed that, similar to 4'-oxoadenosine analogues, at least one hydrogen on the 5'-uronamide moiety was necessary for high-affinity binding at the human A(3) AR, presumably to allow this group to donate a H bond within the binding site. Furthermore, bulky substituents on the 5'-uronamide reduced binding affinity, but in some cases large 5'-uronamide substituents, such as substituted benzyl and 2-phenylethyl groups, maintained moderate affinity with reduced efficacy, leading to A(3) AR partial agonists or antagonists. In several cases for which the corresponding 4'-oxonucleosides have been studied, the 4'-thionucleosides showed higher binding affinity to the A(3) AR. 相似文献
33.
Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer 总被引:3,自引:0,他引:3
Hebbar M Wacrenier A Desauw C Romano O Cattan S Triboulet JP Pruvot FR 《Anti-cancer drugs》2006,17(7):855-857
In patients with metastatic colorectal cancer, the use of cetuximab currently requires a documented tumoral epidermal growth factor receptor positivity. Responses to cetuximab, however, have been described in patients with epidermal growth factor receptor-negative tumors. We have used cetuximab in all eligible patients with metastatic colorectal cancer, whether their tumor expressed epidermal growth factor receptor or not. We assessed the cetuximab efficacy with regard to tumoral epidermal growth factor receptor expression. Twenty patients with metastatic colorectal cancer were treated off study with cetuximab and irinotecan after failure of oxaliplatin- and irinotecan-based regimens. Tumors were analyzed in all patients for epidermal growth factor receptor expression by immunohistochemistry. Tumors were positive for epidermal growth factor receptor in 12 cases and negative in eight cases. An objective response to cetuximab-based therapy was obtained in four patients (20%). Tumors of these four patients were negative for epidermal growth factor receptor expression. These results provide further evidence for the lack of usefulness of epidermal growth factor receptor detection by immunohistochemistry for cetuximab therapy in patients with metastatic colorectal cancer. 相似文献
34.
Hebbar M Ernst O Cattan S Dominguez S Oprea C Mathurin P Triboulet JP Paris JC Pruvot FR 《Oncology》2006,70(2):154-158
OBJECTIVES: We assessed the safety and efficacy of docetaxel, a microtubule inhibitor, in patients with advanced hepatocellular carcinoma (HCC). METHODS: HCC patients that were not suitable for local therapy, but who possessed measurable disease, good performance status and adequate organ function were eligible. Docetaxel was administered every 3 weeks at a dose of 100 mg/m(2) (or 75 mg/m(2) if transaminase levels were between 1.5 and 3.5 times the upper normal limit). Efficacy was assessed radiologically every three cycles of chemotherapy. RESULTS: Fifteen patients were enrolled: 11 males and 4 females; their median age was 64 years (range, 42-72 years). Nine patients had underlying cirrhosis. Four patients had been surgically treated before relapse (liver resection in 3 cases and transplantation in 1), 3 had been treated with arterial chemoembolization and 1 with arterial chemotherapy (doxorubicin). A total of 57 cycles of docetaxel were delivered (median 3, range 1-6). Significant toxicity was observed: mostly grade 3-4 neutropenia and fatigue (6 and 4 patients, respectively). Treatment had to be stopped because of toxicity in 6 patients, all having underlying cirrhosis. An important partial response was obtained in 1 patient, a result that enabled liver transplantation; this patient is still alive after 34 months. Five patients had transient stable disease. CONCLUSION: When used in this schedule, docetaxel does not appear to be safe and effective enough in patients with advanced HCC and cirrhosis. 相似文献
35.
François E Hebbar M Bennouna J Mayeur D Perrier H Dorval E Martin C Bourgeois H Barthélemy P Douillard JY 《Oncology》2005,68(4-6):299-305
PURPOSE: To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas. PATIENTS AND METHODS: Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response. RESULTS: Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis). CONCLUSION: Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients. 相似文献
36.
Vaitla PM Radford PM Tighe PJ Powell RJ McDermott EM Todd I Drewe E 《Arthritis and rheumatism》2011,63(4):1151-1155
In this report, we describe treatment outcomes in the first case of a patient with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) treated with the anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody tocilizumab. Since IL-6 levels are elevated in TRAPS, we hypothesized that tocilizumab might be effective. The patient, a 52-year-old man with lifelong TRAPS in whom treatment with etanercept and anakinra had failed, was administered tocilizumab for 6 months, and the therapeutic response was assessed by measurement of monocyte CD16 expression and cytokine levels. Following treatment, the evolving acute attack was aborted and further attacks of TRAPS were prevented. The patient did not require corticosteroids and showed significant clinical improvement in scores for pain, stiffness, and well-being. Moreover, the acute-phase response diminished significantly with treatment. Monocyte CD16 expression was reduced and the numbers of circulating CD14+CD16+ and CD14++CD16- monocytes were transiently decreased. However, cytokine levels were not reduced. This case supports the notion of a prominent role for IL-6 in mediating the inflammatory attacks in TRAPS, but blockade of IL-6 did not affect the underlying pathogenesis. These preliminary findings require confirmation. 相似文献
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T Conroy M Hebbar J Bennouna M Ducreux M Ychou G Ll��do A Adenis R Faroux C Rebischung L Kockler J Y Douillard 《British journal of cancer》2010,102(1):59-67