全文获取类型
收费全文 | 3834篇 |
免费 | 231篇 |
国内免费 | 21篇 |
专业分类
耳鼻咽喉 | 22篇 |
儿科学 | 124篇 |
妇产科学 | 82篇 |
基础医学 | 623篇 |
口腔科学 | 40篇 |
临床医学 | 368篇 |
内科学 | 983篇 |
皮肤病学 | 75篇 |
神经病学 | 457篇 |
特种医学 | 76篇 |
外科学 | 295篇 |
综合类 | 6篇 |
预防医学 | 156篇 |
眼科学 | 37篇 |
药学 | 315篇 |
中国医学 | 2篇 |
肿瘤学 | 425篇 |
出版年
2023年 | 18篇 |
2022年 | 62篇 |
2021年 | 97篇 |
2020年 | 56篇 |
2019年 | 80篇 |
2018年 | 85篇 |
2017年 | 74篇 |
2016年 | 93篇 |
2015年 | 99篇 |
2014年 | 154篇 |
2013年 | 182篇 |
2012年 | 303篇 |
2011年 | 324篇 |
2010年 | 181篇 |
2009年 | 150篇 |
2008年 | 246篇 |
2007年 | 264篇 |
2006年 | 232篇 |
2005年 | 250篇 |
2004年 | 210篇 |
2003年 | 209篇 |
2002年 | 190篇 |
2001年 | 34篇 |
2000年 | 29篇 |
1999年 | 29篇 |
1998年 | 55篇 |
1997年 | 33篇 |
1996年 | 28篇 |
1995年 | 34篇 |
1994年 | 15篇 |
1993年 | 11篇 |
1992年 | 23篇 |
1991年 | 16篇 |
1990年 | 22篇 |
1989年 | 16篇 |
1988年 | 14篇 |
1987年 | 19篇 |
1986年 | 16篇 |
1985年 | 11篇 |
1984年 | 15篇 |
1983年 | 16篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1973年 | 5篇 |
1971年 | 5篇 |
1970年 | 6篇 |
1969年 | 5篇 |
1966年 | 6篇 |
排序方式: 共有4086条查询结果,搜索用时 15 毫秒
11.
Wessels MW Berger RM Frohn-Mulder IM Roos-Hesselink JW Hoogeboom JJ Mancini GS Bartelings MM Krijger Rd Wladimiroff JW Niermeijer MF Grossfeld P Willems PJ 《American journal of medical genetics. Part A》2005,(2):171-179
Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect. 相似文献
12.
Development and evaluation of a capture ELISA for IgM antibody to the human cytomegalovirus major DNA binding protein. 总被引:6,自引:0,他引:6
M Grazia Revello E Percivalle M Zannino V Rossi G Gerna 《Journal of virological methods》1991,35(3):315-329
A new capture ELISA (ELAb) for determination of the IgM antibody response to the human cytomegalovirus major DNA binding protein (p52) was developed by using a p52-specific monoclonal antibody. As a reference test, a capture ELISA using in parallel viral- and cell-control labeled antigens (ELA) was employed. General specificity, which was determined on 180 unselected IgM-negative sera from an adult population was 100%; stringent specificity, which was evaluated on 108 potentially interfering sera from patients with Epstein-Barr virus infectious mononucleosis, autoimmune diseases, rheumatoid factor or treated with radioimmunotherapy, was 96.3%; finally, clinical specificity, determined on 79 IgM-negative sera drawn prior to onset of primary HCMV infection, was 100%. Thus, the overall specificity was 98.9% (363/367 IgM negative tested sera). Sensitivity assayed on 277 IgM-positive sera was 100%. The study of the kinetics of the IgM antibody response in sequential blood samples from 9 immunocompetent and 9 heart transplanted patients showed that, while in the immunocompetent p52-specific IgM titer fell sharply 2-3 months after onset and was virtually undetectable 12 months after onset, in the immunocompromised the IgM response persisted for longer than a year. Recurrent HCMV infections were associated with a high titer IgM response in 6 (30%), and with a low IgM response in another 6 (30%) heart transplanted patients within a group of 20 patients sequentially examined. Finally, IgM antibodies were detected in all 4 infants with congenital infection and in 5 of 6 infants with neonatal infection. The results show that the HCMV p52-specific IgM antibody response parallels that obtained by ELA, thus representing a major component of it. ELAb is highly sensitive, specific and reproducible. It represents a major advance among capture ELISA techniques, allowing detection of IgM antibody reactive to a specific viral protein. 相似文献
13.
Angelo Passerini Liliana Strada Marina Grisoli Maurizio Sberna Maria Grazia Bruzzone 《Child's nervous system》1990,6(1):33-36
The spin-echo procedure is the basic technique in a magnetic resonance (MR) study (the magnetization vector is flipped by 90° onto the ortogonal plane to the main magnetic field). Very soon after the MR procedure was developed, it was pointed out how important it is to achieve the needed contrast with shorter repetition times (TRs) to reduce the imaging time. Recently, fast imaging techniques have been introduced (partial flip angles, short TRs, and the lack of 180° radiofrequency pulses to refocus the spins are their main characteristics; the spins are refocused by the application of a gradient reversal technique). These techniques are particularly needed in pediatric neuroradiology, where the examination time must be as short as possible. At present, partial flip-angle techniques are almost completely replacing the conventional spin-echo procedure, but the variations in flip angle could result in a change in contrast. For these reasons, conventional spin-echo techniques may still be useful in a routine MR study.Presented at the 11th Meeting of the European Society for Paediatric Neurosurgery, Naples 1988 相似文献
14.
Dr. Maurizio Vaglini MD Dr. Filiberto Belli MD Mario Santinami MD Flavio Arienti MD Giorgio Parmiani MD Laura Persiani MD Nicola Santoro MD Maria Grazia Inglese MD Fortunato D'Elia MD Natale Cascinelli MD 《Annals of surgical oncology》1995,2(1):61-70
Background: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy.
Methods: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9–12 × 106 IU/M2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8–28 × 109) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9–12×106 IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP.
Results: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues.
Conclusions: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment. 相似文献
15.
Francesco Castelli Maria Grazia Sarpietro Chiara Messina Alessandra De Lazzari Dario Di Rosa Antonino Giannetto 《European journal of pharmaceutical sciences》2003,19(4):237-243
Nimesulide release from micronized and unmicronized drug particles was tested at pH 7.4 by measuring the transfer to dimyristoylphosphatidylcholine liposomes (multilamellar and unilamellar vesicles), chosen as a biomembrane model. The perturbing effect of increasing molar fractions of pure nimesulide on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes was investigated by differential scanning calorimetry. In order to study the drug dissolution process by its uptake into void liposomes, measurements were carried out on suspensions of blank liposomes added to weighed amounts of free powdered nimesulide (micronized and unmicronized). The amount of drug transferred was quantified by comparing the effect caused by the dissolved and released drug to that caused by the free drug that had been previously molecularly dissolved in the liposomes. The calorimetric results show that the dissolution rate depends on the nimesulide form (micronized or unmicronized), and that the transfer to the void liposomes is quicker when the drug is in a micronized form. The uptake was faster when unilamellar vesicles were used instead of multilamellar vesicles because of the greater lipid surface. The calorimetric technique could represent an alternative 'in vitro' method that can be applied to the study of the dissolution kinetics directly at the site of drug uptake, mimicking a biological system. 相似文献
16.
Grazia Arpino Stephanie J Green D Craig Allred Dannika Lew Silvana Martino C Kent Osborne Richard M Elledge 《Clinical cancer research》2004,10(17):5670-5676
PURPOSE: Preclinical data indicate that expression of the ErbB family of receptors, such as HER-2 and HER-1 (EGFR) may be involved in endocrine resistance. Evidence of resistance from clinical studies has been inconsistent. The present study examined whether HER-2 gene amplification or HER-1 expression predicted response to tamoxifen. PATIENTS AND METHODS: Three hundred and forty nine patients had estrogen receptor (ER)-positive breast cancer and received daily tamoxifen as initial therapy for advanced disease. HER-2 gene amplification, detected by fluorescence in situ hybridization, and HER-1 expression, evaluated by immunohistochemistry, was determined on 136 and 204 patients, respectively. RESULTS: HER-2 amplification was correlated with lower ER (P = 0.02), HER-1 positivity (P = 0.004), and HER-2 protein overexpression (P < 0.00001). The response rate was 56% for HER-2 non-amplified versus 47% for HER-2 amplified tumors (P = 0.38), and 58% for HER-1-negative versus 36% for HER-1-positive (P = 0.05). Time to treatment failure (TTF) was 7 months for non-amplified HER-2 tumors and 5 months (P = 0.007) for amplified HER-2 tumors, and there was a trend toward a better overall survival (OS) in patients with non-amplified HER-2 tumors (median 31 versus 25 months, respectively, P = 0.07). For positive versus negative HER-1 tumors, TTF was 4 versus 8 months (P = 0.08) and median survival was 24 versus 31 months (P = 0.41). Combining HER-1 expression and HER-2 gene status, patients with both negative HER-1 expression and non-amplified HER-2 had longer TTF (P = 0.001) and OS (P = 0.03) than if either were positive. In multivariate analysis, HER-2 was not an independent factor for TTF and OS, although HER-1 was significant for TTF only (P = 0.001). CONCLUSION: Patients with HER-2 amplification and HER-1 expression had lower ER levels and were modestly less responsive to tamoxifen, suggesting that molecular events in addition to those involving the ErbB receptors are important in determining the endocrine-resistant phenotype. 相似文献
17.
E Biganzoli P Boracchi D Coradini M Grazia Daidone E Marubini 《Annals of oncology》2003,14(10):1484-1493
BACKGROUND: The present study investigated complex time-dependent effects of routinely assessed factors on the risk of breast cancer recurrence over follow-up time, with a partial logistic artificial neural network (PLANN) model. PATIENTS AND METHODS: PLANN was applied to data from 1793 patients with node-negative breast cancer, not submitted to any adjuvant treatment and with a minimal potential follow-up of 10 years. RESULTS: The shape of the hazard function changed according to histology, which showed a time-dependent effect, partly modulated by estrogen receptors (ERs). Age and progesterone receptors (PgR) showed protective effects; the latter was more evident for short follow-up and high ER values. Tumour size and ER content showed time-dependent unfavourable effects at early and long follow-up times, respectively. Predicted values of disease recurrence probability at 2 years of follow-up showed that low steroid-receptor content, young age and large tumour size were associated with the highest risk of relapse. Although the oldest patients with high ER content seem to be those most protected overall, high risk predictions tend to spread also to higher steroid-receptor contents, intermediate ages and small tumour size, with an increase in follow-up time. CONCLUSION: PLANN with suitable visualisation techniques provided thorough insights into the dynamics of breast cancer recurrence for improving individual risk staging of node-negative breast cancer patients. 相似文献
18.
19.
Luisa Di Marzio Alfredo Di Leo Benedetta Cinque Donatella Fanini Alessio Agnifili Pasquale Berloco Michele Linsalata Dionigi Lorusso Michele Barone Claudio De Simone Maria Grazia Cifone 《Cancer epidemiology, biomarkers & prevention》2005,14(4):856-862
OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms. 相似文献
20.
Andrea Pession Maria Grazia Valsecchi Giuseppe Masera Willem A Kamps Edina Magyarosy Carmelo Rizzari Elisabeth R van Wering Luca Lo Nigro Anna van der Does Franco Locatelli Giuseppe Basso Maurizio Aricò 《Journal of clinical oncology》2005,23(28):7161-7167
PURPOSE: Between September 1991 and May 1997, within the International Berlin-Frankfurt-Muenster Study Group (I-BFM-SG), a randomized study was performed aimed at assessing the efficacy of prolonged use of high-dose l-asparaginase (HD-l-ASP) during continuation therapy in children with standard risk (SR) acute lymphoblastic leukemia (ALL), treated with a reduced BFM-type chemotherapy. PATIENTS AND METHODS: The Italian, Dutch, and Hungarian groups participated in this study denominated IDH-ALL-91, and 494 children were enrolled. Treatment consisted of a BFM-type modified backbone with omission of the IB part in induction and elimination of two doses of anthracyclines during reinduction in both arms at the beginning of continuation therapy. Patients were randomly assigned to receive (YES-ASP) or not (NO-ASP) 20 weekly HD-l-ASP (25,000 IU/m2). RESULTS: The event-free-survival and overall survival probabilities at 10 years for the entire group were 82.5% (1.8) and 90.3% (1.3), respectively. Of the 490 patients eligible for random assignment, 355 (72.4%) were randomly assigned (178 YES-ASP and 177 NO-ASP). After a median follow-up of 9 years, the probability of disease-free survival at 10 years was 87.5% (SE, 2.5) for YES-ASP arm versus 78.7% (SE, 3.3) for NO-ASP arm (P = .03). In multivariate analysis, NO-ASP arm (P = .03), male sex (P = .004), and age older than 10 years (P = .0003) had a significantly adverse impact on outcome. CONCLUSION: In this subset of patients, selected with criteria not including monitoring of minimal residual disease, application of extended HD-l-ASP may improve prognosis, compensating reduced leukemia control that results from adoption of a reduced-intensity BFM-backbone for treatment of children with SR ALL. 相似文献