全文获取类型
收费全文 | 14603篇 |
免费 | 874篇 |
国内免费 | 71篇 |
专业分类
耳鼻咽喉 | 71篇 |
儿科学 | 548篇 |
妇产科学 | 348篇 |
基础医学 | 2037篇 |
口腔科学 | 254篇 |
临床医学 | 1429篇 |
内科学 | 3111篇 |
皮肤病学 | 367篇 |
神经病学 | 1467篇 |
特种医学 | 315篇 |
外科学 | 1501篇 |
综合类 | 85篇 |
一般理论 | 16篇 |
预防医学 | 1201篇 |
眼科学 | 298篇 |
药学 | 971篇 |
中国医学 | 25篇 |
肿瘤学 | 1504篇 |
出版年
2024年 | 19篇 |
2023年 | 161篇 |
2022年 | 277篇 |
2021年 | 506篇 |
2020年 | 307篇 |
2019年 | 432篇 |
2018年 | 472篇 |
2017年 | 379篇 |
2016年 | 379篇 |
2015年 | 471篇 |
2014年 | 616篇 |
2013年 | 795篇 |
2012年 | 1236篇 |
2011年 | 1160篇 |
2010年 | 690篇 |
2009年 | 582篇 |
2008年 | 986篇 |
2007年 | 992篇 |
2006年 | 945篇 |
2005年 | 861篇 |
2004年 | 827篇 |
2003年 | 768篇 |
2002年 | 617篇 |
2001年 | 71篇 |
2000年 | 61篇 |
1999年 | 93篇 |
1998年 | 111篇 |
1997年 | 95篇 |
1996年 | 86篇 |
1995年 | 64篇 |
1994年 | 52篇 |
1993年 | 59篇 |
1992年 | 46篇 |
1991年 | 38篇 |
1990年 | 20篇 |
1989年 | 22篇 |
1988年 | 22篇 |
1987年 | 21篇 |
1986年 | 17篇 |
1985年 | 25篇 |
1984年 | 23篇 |
1983年 | 18篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 15篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1972年 | 7篇 |
1966年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
Andrea Bonetti Marta Zaninelli Stefania Rodella Annamaria Molino Loris Sperotto Quirino Piubello Franco Bonetti Rolando Nortilli Monica Turazza Gian Luigi Cetto 《Breast cancer research and treatment》1996,38(3):289-297
Summary The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( 25% of stained cells) or high (> 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3–58).Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analy-sis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.Presented in part at the Annual Meeting of the American Society of Clinical Oncology, May 14–17, 1994, Dallas, TX, USA 相似文献
62.
During the period May 1989 to November 1990, at the "O. Alberti" Radium Institute of Brescia's General Hospital, 35 patients affected by epidermoid head and neck carcinoma were treated every 28 days with the salvage chemotherapy regimen EMB (epirubicin, 50 mg/m2 i.v. day 1; methotrexate, 40 mg/m2. i.v. days 1, 18; bleomycin, 10 mg/m2 i.v. days 4, 11, 18). Sixteen patients had been previously treated with surgery, 15 with radiotherapy and 4 with chemotherapy. Six patients (Group A) received only 1 cycle of chemotherapy because of disease progression and subsequent death. In another 15 patients (Group B) it was possible to administer 2 cycles of EMB, and 9 of them showed local disease progression and died. Among the remaining 6 patients, evaluated as PR, 1 refused further therapy and 5 were amenable to a previously impossible radiotherapy (4 of them are still alive). Fourteen patients received 3 or more cycles of EMB (Group C): 8 subjects showed progression and died; 1 reached CR and is alive without any evidence of tumor; 5 are in PR (3 of them underwent subsequent radiotherapy and 1 chemotherapy with CDDP). Out of 35 patients, 12 (34%) reached a favorable response (CR or PR) and 8 (22%) are still alive. As regards toxicity, the following adverse events were recorded (< or = 2 Miller's scale): leukopenia (8.5%), thrombocytopenia (5.7%), anemia (14.2%), stomatitis (5.7%), vomiting (5.7%), alopecia (8.5%), and fever (11.4%). It can be concluded that the EMB regimen is very well tolerated and shows good effects in the treatment of patients with relapsed head and neck carcinoma. 相似文献
63.
Fredrik Wiklund Bj?rn-Anders Jonsson Anthony J Brookes Linda Str?mqvist Jan Adolfsson Monica Emanuelsson Hans-Olov Adami Katarina Augustsson-B?lter Henrik Gr?nberg 《Clinical cancer research》2004,10(21):7150-7156
PURPOSE: The RNASEL gene has been proposed as a candidate gene for the HPC1 locus through a positional cloning and candidate gene approach. Cosegregation between the truncating mutation E265X and disease in a hereditary prostate cancer (HPC) family and association between prostate cancer risk and the common missense variant R462Q has been reported. To additionally evaluate the possible role of RNASEL in susceptibility to prostate cancer risk, we performed a comprehensive genetic analysis of sequence variants in RNASEL in the Swedish population. EXPERIMENTAL DESIGN: Using 1624 prostate cancer cases and 801 unaffected controls, the truncating mutation E265X and five common sequence variants, including the two missense mutations R462Q and D541E, were evaluated for association between genotypes/haplotypes and prostate cancer risk. RESULTS: The prevalence of E265X carriers among unaffected controls and prostate cancer patients was almost identical (1.9 and 1.8% in controls and cases, respectively), and evidence for segregation of E265X with disease was not observed within any HPC family. Overall, the analyses of common sequence variants provided limited evidence for association with prostate cancer risk. We found a marginally significant inverse association between the missense mutation D541E and sporadic prostate cancer risk (odds ratio, 0.77; 95% confidence interval, 0.59-1.00) and reduced risk of prostate cancer in carriers of two different haplotypes being completely discordant. CONCLUSIONS: Considering the high quality in genotyping and the size of this study, these results provide solid evidence against a major role of RNASEL in prostate cancer etiology in Sweden. 相似文献
64.
HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2 expression. 总被引:6,自引:0,他引:6
Gennaro Chiappetta Gerardo Botti Mario Monaco Rosa Pasquinelli Francesca Pentimalli Maurizio Di Bonito Giuseppe D'Aiuto Monica Fedele Rodolfo Iuliano Emiliano A Palmieri Giovanna Maria Pierantoni Vincenzo Giancotti Alfredo Fusco 《Clinical cancer research》2004,10(22):7637-7644
We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P=0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer. 相似文献
65.
66.
Donato Gemmati Alessia Ongaro Gian L Scapoli Matteo Della Porta Silvia Tognazzo Maria L Serino Eros Di Bona Francesco Rodeghiero Giuseppe Gilli Roberto Reverberi Angelo Caruso Michela Pasello Agnese Pellati Monica De Mattei 《Cancer epidemiology, biomarkers & prevention》2004,13(5):787-794
Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation. 相似文献
67.
The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer. 总被引:6,自引:0,他引:6
68.
James D. Goldberg MD Monica M. Wohlferd MS 《American journal of obstetrics and gynecology》1997,176(6):1349-1353
OBJECTIVE: Chromosomal mosaicism has been reported in about 1% to 3% of chorionic villus sampling specimens. This report provides incidence and outcome information that should be useful in counseling patients found to have mosaicism on chorionic villus sampling.STUDY DESIGN: A retrospective analysis of 11,200 consecutive patients undergoing chorionic villus sampling at the University of California, San Francisco, during the period from Jan. 1, 1984, to June 1, 1996, was undertaken.RESULTS: A total of 140 cases of mosaicism were identified for an incidence of 1.3%. Follow-up information was available for 130 cases, 26 of which (20%) were confirmed in fetal tissue. Confirmation rates for specific types of mosaicism were as follows: autosomal trisomy 7.6%, sex chromosome 25%, structural abnormality 27.3%, and marker chromosome 77.8%. Neonatal outcome was normal in all cases for which pregnancy continued.CONCLUSION: The data indicate that in most cases of chromosomal mosaicism found by chorionic villus sampling the mosaicism is unlikely to be clinically significant in the fetus. (Am J Obstet Gynecol 1997;176:1349-53.) 相似文献
69.
Bone marrow micrometastases in 109 breast cancer patients: Correlations with clinical and pathological features and prognosis 总被引:5,自引:0,他引:5
Annamaria Molino Giuseppe Pelosi Monica Turazza Loris Sperotto Andrea Bonetti Rolando Nortilli Giovanni Fattovich Cristoforo Alaimo Quirino Piubello Flavia Pavanel Rocco Micciolo Gian Luigi Cetto 《Breast cancer research and treatment》1997,42(1):23-30
Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery. 相似文献
70.
In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems 总被引:7,自引:0,他引:7
Simona Romanelli Paola Perego Graziella Pratesi Nives Carenini Monica Tortoreto Franco Zunino 《Cancer chemotherapy and pharmacology》1998,41(5):385-390
Topotecan, a camptothecin analogue, is a␣specific inhibitor of topoisomerase I approved for use in the treatment of patients
with refractory ovarian carcinoma. The drug's mechanism of action suggests a potential efficacy of drug combinations incorporating
DNA-damaging agents. In an attempt better to define a␣rational basis for drug combination we examined the effect of topotecan
on the cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system growing in vitro and in vivo as a tumor
xenograft. The in vitro cell system included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant subline,
IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal function of the wild-type gene of the parental cell
line. This cell system was chosen since the cell sensitivity to DNA-damaging agents appears to be dependent on p53 gene status.
Cytotoxicity was assessed by the growth inhibition assay using different schedules: (a) a 1-h period of cisplatin exposure
followed by a 24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to cisplatin and topotecan. In the case
of the sequential schedule, an additive interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the simultaneous
schedule was used, a synergistic interaction, more evident for the cisplatin-sensitive cells, was found. On the basis of these
observations at a cellular level, the effect of concomitant administration of the two drugs (i.e., the most favorable schedule)
was studied in the IGROV-1 tumor xenograft, which is moderately responsive to cisplatin and topotecan. Suboptimal doses of
each drug (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable with or superior to that of the
optimal dose of a single treatment (tumor weight inhibition, 60%), thus indicating a␣pharmacological advantage of the combination
over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg) was associated with an evident increase
in the toxicity of the combination, thereby suggesting that the drug interaction was not tumor-specific. Although the molecular
basis of the drug interaction is not clear, it is likely that inhibition of topoisomerase I affects the ability of cells to
repair cisplatin adducts. Such findings may have pharmacological implications since they suggest the potential clinical interest
of topoisomerase I inhibitors in combination with cisplatin.
Received: 14 June 1997 / Accepted: 18 September 1997 相似文献