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701.
Twenty-one patients with recurrent epithelial ovarian carcinoma not amenable to cure with further surgery or radiotherapy were entered into a Phase II trial utilizing i.v. leucovorin at 20 mg/m2 followed by i.v. 5-fluorouracil at 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. Twenty-one patients were entered. Of these, 20 were eligible for toxicity assessment and 19 for response. Five had received prior radiotherapy, and all had received prior cisplatin-based chemotherapy. There was one patient response (5.3%; 95% confidence intervals for response of 0% to 26%). Toxicity was moderate with 5 of 20 (25%) grade 3 or 4 leukopenia, 12 of 20 (60%) grade 3 or 4 granulocytopenia, 1 of 20 (5%) grade 3 thrombocytopenia, 5 of 20 (25%) grade 3 GI toxicity, and 2 of 20 (10%) grade 3 neurotoxicity. There was one toxic death in a patient who developed granulocytopenia and pneumonia after her third course of treatment. This dose schedule of 5-fluorouracil and leucovorin has minimal activity in patients with recurrent epithelial ovarian carcinoma who have received prior cisplatin chemotherapy. 相似文献
702.
703.
Ubiquitin-positive Lewy neurites and Lewy bodies are found in idiopathic Parkinson's disease (PD) and diffuse Lewy body disease
(DLBD). We found that, in three patients with PD and one with DLBD, microtubule-associated protein 5 (MAP5) immunostaining
was consistently present in both Lewy neurites and Lewy bodies throughout the brainstem and forebrain regions affected in
the disease. In contrast, other cytoskeletal markers (neurofilaments and MAP2) could be demonstrated in only a small fraction
of Lewy bodies and neurites. Confocal microscopy demonstrated that MAP5 immunolabeling was located around the perimeter of
the ubiquitin-positive labeling which occupied the central region of the neurite and Lewy body, with some overlap between
MAP5 and ubiquitin staining. In contrast, in those Lewy bodies and neurites immunopositive for phosphorylated and non-phosphorylated
neurofilament proteins, the neurofilament labeling was quite peripheral to the ubiquitin staining, with little or no overlap.
Our results suggest MAP5 is more closely associated with the ubiquitinated proteins of Lewy bodies and neurites than other
cytoskeletal proteins.
Received: 3 July 1995 / Revised, accepted: 8 September 1995 相似文献
704.
Katherine Y. Look M.D. John A. Blessing Ph.D. Fidel A. Valea M.D. Ramon McGehee M.D. Alberto Manetta M.D. Kenneth D. Webster M.D. Willie A. Andersen M.D. 《Gynecologic oncology》1997,67(3):255-258
Objective.The objective of the study was to determine the response rate and associated toxicity of 5-fluorouracil and high-dose leucovorin in patients with recurrent adenocarcinoma of the cervix.Methods.Between December 1993 and October 1995, 53 patients with recurrent adenocarcinoma of the cervix were entered into a Phase II trial utilizing 200 mg/m2of intravenous (iv) leucovorin with 370 mg/m2of iv 5-fluorouracil daily for 5 days every 4 weeks for two courses, then every 5 weeks until disease progression. Eligibility criteria were a Gynecologic Oncology Group (GOG) performance status of 0–2, adequate bone marrow reserve, adequate liver function with bilirubin ≤ 1.5× normal and SGOT and alkaline phosphatase ≤ 3× normal, serum creatinine ≤ 2 mg%, and signed informed consent. Standard GOG toxicity and response criteria were employed.Results.Six patients were ineligible because of wrong cell type (N= 3), insufficient pathology materials (N= 2), or a second primary (N= 1); therefore 45 were evaluable for toxicity. Two patients did not have adequate response assessment; thus, 43 were evaluable for response. The median age was 50 (range, 28–79). Prior chemotherapy had been administered to 16 patients and radiotherapy to 40 patients. The median number of courses delivered was three (range, 1–22). The site of evaluable disease was pelvic in 25 patients and extra–pelvic in 18. Grade 3 neutropenia was seen in 17.8% (8/45) patients and 35.5% (16/45) developed grade 4 neutropenia. Grade 3 or 4 thrombocytopenia was seen in 1 patient each (2.1%). Grade 3 gastrointestinal toxicity with nausea, vomiting, diarrhea, dehydration, or stomatitis was of grade 3 severity in 11.1% (5/45) and grade 4 in 6.7% (3/45). There were four partial responses and two complete responses for an overall response rate of 14%. The duration of the complete responses was 17.3 and 8.8+ months. None of the patients with responses had previously received chemotherapy.Conclusion.The schedule of 5-fluorouracil and leucovorin exhibits moderate activity in patients with previously treated adenocarcinoma of the cervix and should be considered for a trial in chemotherapy-naive patients. 相似文献
705.
Gregory P. Sutton John A. Blessing Mark D. Adelson Parviz Hanjani 《Investigational new drugs》1990,8(4):377-379
Summary A phase II trial of vinblastine in patients with refractory epithelial ovarian adenocarcinoma of the ovary was conducted by the Gynecologic Oncology Group (GOG) between March 9, 1988 and July 7, 1988. Vinblastine was administered in a dose of 9 mg/m2 intravenously every three weeks until disease progression or toxicity supervened. Twenty patients were entered initially. One was ineligible due to a previous primary cancer. Thus, 19 patients are evaluable for toxicity and response. All patients had cisplatin-combination chemotherapy and four had prior radiotherapy. Median age was 63 years (range 40–75 years). Thirteen patients had disease in the pelvis and six had extrapelvic metastases. Ten patients had grade 3 lesions and seven had grade 2. A median of two courses (range: 1–6) were administered. Toxicity was moderate. Seven patients (36.8%) experienced GOG grade 3 or 4 leukocytopenia and six had grade 3 or 4 granulocytopenia. Median nadir WBC was 2,000 cells/1 (range 600–3,500) and platelet nadirs for the three patients with thrombocytopenia were 60,000, 116,000, and 147,000. Other toxicity included grade 3 gastrointestinal and renal toxicity in one patient each. Seven patients (36.8%) had stable disease on therapy and 12 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in patients with resistant epithelial ovarian adenocarcinoma progressing on first-line chemotherapy.
Responsible author: Dr. Gregory P. Sutton, Indiana University Medical Center, Section of Gyn. Oncology, Dept. of Obstetrics & Gynecology, 926 West Michigan Street, Indianapolis, IN 46223, USA. 相似文献
706.
707.
David H Moore John A Blessing Richard P McQuellon Howard T Thaler David Cella Jo Benda David S Miller George Olt Stephanie King John F Boggess Thomas F Rocereto 《Journal of clinical oncology》2004,22(15):3113-3119
PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL. 相似文献
708.
The role of adjuvant therapy in Stage I ovarian cancer 总被引:1,自引:0,他引:1
M M Hreshchyshyn R C Park J A Blessing H J Norris D Levy L D Lagasse W T Creasman 《American journal of obstetrics and gynecology》1980,138(2):139-145
Women with Stage I epithelial carcinoma of the ovary were initially treated by an extirpative operation and were subsequently randomized to either no further treatment, radiotherapy, or chemotherapy. Only two patients (6%) treated with chemotherapy developed recurrence, compared to five (17%) and seven (30%) patients in the no-treatment and radiotherapy regimens, respectively (P < 0.05). All patients, with the possible exception of those with Stage IA(1)g1, appeared to benefit from adjuvant chemotherapy compared to no treatment or radiotherapy. 相似文献
709.
Storch A Blessing H Bareiss M Jankowski S Ling ZD Carvey P Schwarz J 《Molecular pharmacology》2000,57(3):589-594
Inhibition of catechol-O-methyltransferase (COMT; EC 2.1.1.6) is a new therapeutic strategy in the treatment of Parkinson's disease. However, nothing is known about the effects of COMT inhibition on levodopa (L-dopa)-induced toxicity in dopamine (DA) neurons. Therefore we evaluated the effects of the selective COMT inhibitors Ro 41-0960, OR-486, and tolcapone alone and in combination with L-dopa in primary mesencephalic cultures from rat. Neither COMT inhibitor affected the growth of tyrosine hydroxylase immunoreactive (THir) cells with concentrations up to 10 microM when studied alone. However, Ro 41-0960 reduced the L-dopa-induced THir cell loss after 24 h in a dose-dependent manner, shifting the TD(50) value from 21 microM in the absence to 71 microM in the presence of 1 microM Ro 41-0960 (P <.01) without affecting survival of non-DA neurons. OR-486 and the clinically used COMT inhibitor tolcapone showed similar effects. In contrast, toxicity induced by D-dopa was not altered by COMT inhibitors. Furthermore, the primary metabolite of L-dopa formed by COMT, 3-O-methyldopa, and the methyl group donor S-adenosyl-L-methionine used by COMT did not alter THir neuron survival and L-dopa-induced toxicity, respectively, with concentrations up to 100 microM. These data demonstrate that COMT inhibition attenuates L-dopa toxicity toward DA neurons in vitro, but probably not by preventing 3-O-methyldopa production or cellular S-adenosyl-L-methionine depletion. 相似文献
710.
J T Thigpen J A Blessing H Ball P Hanjani A Manetta H Homesley 《Gynecologic oncology》1988,31(3):435-438
Thirty-eight patients with advanced or recurrent carcinoma of the endometrium who had received no prior chemotherapy were placed on study by the Gynecologic Oncology Group. One was deemed histologically ineligible. Three patients had insufficient trials to evaluate response. Of the remaining 34 who received hexamethylmelamine 280 mg/m2 orally daily on Days 1 through 14 of each 4-week course, there were only three objective responses, two complete and one partial. Although toxicity was tolerable, hexamethylmelamine has minimal activity in advanced or recurrent endometrial carcinoma at the dose and schedule tested. 相似文献