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101.
Randa El-Zein Nivea Conforti-Froes William W. Au 《Environmental and molecular mutagenesis》1997,30(2):196-204
Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (<30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (<30 pack-years), the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% CL = 0.46–40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variations in cancer outcome, to identify high risk individuals and to assess health risk. Environ. Mol. Mutagen. 30:196–204, 1997. © 1997 Wiley-Liss, Inc. 相似文献
102.
Asthma phenotypes based on health services use for allergic diseases in a province-wide birth cohort
Miceline Mésidor Andrea Benedetti Mariam El-Zein Dick Menzies Marie-Élise Parent Marie-Claude Rousseau 《Annals of allergy, asthma & immunology》2019,122(1):50-57.e2
Background
Many previous studies on asthma phenotypes were conducted in selected clinical populations and overlooked changes throughout the life course.Objective
To identify asthma phenotypes based on use of health services for allergic diseases in 3 life periods and document transitions among phenotypes across life periods.Methods
In a population-based cohort of 78,211 individuals born in 1974 in the province of Québec, Canada, we documented medical visits and hospitalizations for asthma and other allergic diseases until 1994. Phenotypes based on clusters of health services use in childhood (8-12 years of age), adolescence (13-17 years of age), and young adulthood (18-20 years of age) were identified using a hierarchical method among 9,989 individuals (12.8%) who had at least one health encounter for asthma during follow-up. Population-level probabilities of transitioning among phenotypes were estimated in the full study population.Results
In the subset with asthma, 6 phenotypes were identified during both childhood and young adulthood and 7 during adolescence. The most common phenotype was no asthma or allergic diseases: 58% in childhood, 42% in adolescence, and 54% in adulthood. The second most common was the mild asthma and no allergic diseases phenotype, representing 36%, 31%, and 21%, respectively, in these 3 periods. In the study population, 87% of the individuals remained in the no asthma phenotype group during the follow-up. Most individuals in the asthma phenotypes transitioned over time.Conclusion
Our study uniquely contributes to a better understanding, at the population level, of the manifestations and transitions in asthma phenotypes during the life course. 相似文献103.
S. Magnan J.E. Tota M. El-Zein A.N. Burchell J.T. Schiller A. Ferenczy P.-P. Tellier F. Coutlée E.L. Franco 《Clinical microbiology and infection》2019,25(2):210-216
Objectives
To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women.Methods
We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed.Results
Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9–13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45–0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels.Conclusions
Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women. 相似文献104.
Deng CZ Fons MP Rosenblatt J El-Zein RA Abdel-Rahman SZ Albrecht T 《Environmental and molecular mutagenesis》2006,47(3):150-161
The modulating effect of acute exposure to NiCl2 on the induction of chromosome aberrations by a model carcinogen, benzo[a]pyrene (B[a]P), was examined in Chinese hamster V79 lung cells. At concentrations up to 20 microg/ml (84.2 microM), NiCl2 did not significantly increase the frequency of chromosome aberrations in V79 cells when the cells were exposed concomitantly to 0.5 microg/ml B[a]P. Addition of the S15 liver microsomal fraction together with the B[a]P did not alter the results. Addition of NiCl2 2 hr before treatment of cells with 0.5 microg/ml B[a]P also did not result in a significant elevation of the frequency of chromosome aberrations, even at NiCl2 concentrations as high as 20 microg/ml. Contrasting sharply with these findings, when V79 cells were treated with NiCl2 immediately after B[a]P exposure, a significant increase in the frequency of chromosome damage was observed at NiCl2 concentrations as low as 5 microg/ml (21.1 microM). NiCl2-mediated enhancement of chromosome damage was also observed when V79 cells were exposed to the reactive B[a]P intermediate, benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE). In the BPDE-treated cells, the level of NiCl2-mediated enhancement was similar to that observed with the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA, 100 ng/ml). These results are consistent with the view that the effect of nickel (II) on B[a]P-induced genetic damage is dependent on the relative times of exposure to Ni2+ and B[a]P. NiCl2 did not enhance the frequency of chromosome aberrations induced by Chromium (VI), regardless of the order of addition of the chemicals to the V79 cells. These results suggest that nickel may act as a promoter of chemically-induced genetic damage through induction of error-prone repair. 相似文献
105.
目的:了解不同级别慢性阻塞性肺病患者肺泡毛细血管膜弥散量和肺泡毛细血管血量的特点。方法:收集2006-07/2007-03就诊于四川大学华西医院呼吸科的慢性阻塞性肺病患者154例,依据慢性阻塞性肺病方案分级,0级64例,Ⅰ级38例,Ⅱ级26例,Ⅲ和Ⅳ级共26例。行肺通气功能、肺容量、一氧化碳弥散量、肺泡毛细血管膜弥散量和肺泡毛细血管血量测定。结果:154例患者均进入结果分析。①0级与I级慢性阻塞性肺病患者,无论一氧化碳弥散量、肺泡毛细血管膜弥散量和肺泡毛细血管血量都正常。随着慢性阻塞性肺病程度加重,一氧化碳弥散量、肺泡毛细血管膜弥散量和肺泡毛细血管血量均有不同程度降低。Ⅱ级慢性阻塞性肺病时一氧化碳弥散量和肺泡毛细血管膜弥散量下降明显,肺泡毛细血管血量改变不明显。其中肺泡毛细血管膜弥散量出现异常明显早于一氧化碳弥散量和肺泡毛细血管血量,而且较严重。Ⅲ和Ⅳ级慢性阻塞性肺病的肺泡毛细血管血量下降明显。②一氧化碳弥散量、肺泡毛细血管膜弥散量和肺泡毛细血管血量与慢性阻塞性肺病级别、残气量/肺总量成负相关,与第1秒用力呼气容积/用力肺活量和第1秒用力呼气容积占预计值百分比成正相关,而且,肺泡毛细血管膜弥散量与各指标的相关性最好。结论:随着慢性阻塞性肺病程度的加重,一氧化碳弥散量、肺泡毛细血管膜弥散量和肺泡毛细血管血量均有下降。肺泡毛细血管膜弥散量的异常比一氧化碳弥散量和肺泡毛细血管血量较早出现而且较严重。肺泡毛细血管膜弥散量的测定可以监测疾病发展并早期发现慢性阻塞性肺病气体交换的异常。 相似文献
106.
Eliya Farah Rami Ali Parker Tope Mariam El-Zein Eduardo L. Franco 《Current oncology (Toronto, Ont.)》2021,28(2)
(1) Background: Preventive measures taken in response to the coronavirus disease 2019 (COVID-19) pandemic have adversely affected an entire range of cancer-related medical activities. The reallocation of medical resources, staff, and ambulatory services, as well as critical shortages in pharmaceutical and medical supplies have compelled healthcare professionals to prioritize patients with cancer to treatment and screening services based on a set of classification criteria in cancer-related guidelines. Cancer patients themselves have been affected on multiple levels, and addressing their concerns poses another challenge to the oncology community. (2) Methods: We conducted a Canada-wide search of cancer-related clinical practice guidelines on the management and prioritization of individuals into treatment and screening services. We also outlined the resources provided by Canadian cancer charities and patient advocacy groups to provide cancer patients, or potential cancer patients, with useful information and valuable support resources. (3) Results: The identified provincial guidelines emphasized cancer care (i.e., treatment) more than cancer control (i.e., screening). For cancer-related resources, a clear significance was placed on knowledge & awareness and supportive resources, mainly relating to mental health. (4) Conclusion: We provided a guidance document outlining cancer-related guidelines and resources that are available to healthcare providers and patients across Canada during the COVID-19 pandemic. 相似文献
107.
El-Zein R Albrecht T Knutson E Legator MS Abdel-Rahman SZ 《Archives of environmental & occupational health》2007,62(3):161-163
Little is known about the mechanism by which ethylene glycol monomethyl ether (EGME) produces genotoxic effects in humans. The authors found that individuals exposed in utero to EGME showed characteristic dysmorphic features, unexplained mental retardation, and persistent cytogenetic damage. They hypothesized that these individuals had a higher level of terminal chromosome arrangements, accounting for the genomic instability detected. Results indicate that in utero-exposed individuals have significantly reduced telomeres relative to non-in utero-exposed participants. The M +/- SEM pixel intensity in the in utero-exposed participants was 43.6 +/- 7.6 compared with 74.1 +/- 1.9 in the non-in utero-exposed. Findings suggest that exposure to EGME in utero could result in terminal chromosome rearrangements and shortening of telomere length, leading to the observed dysmorphic features and idiopathic mental retardation. 相似文献
108.
Ellen Swartwout Ashley El-Zein Patricia Deyo Rachel Sweenie Randi Streisand 《Current diabetes reports》2016,16(7):59
With the growing prevalence of diabetes in teens and frequent concomitant problems with adherence, adolescents are a frequent target for diabetes self-management support and education. Due to widespread use of technology among teens in general, the use of serious games, games used for purposes beyond entertainment with the intention to educate and support health behavior for teens with diabetes self-management, is an emerging and promising practice. This report explores games intended for teens with diabetes, how the use of games may enhance clinical practice, and provides suggestions for future research and better utilization of these technologies. Current research on the use of gaming for promoting diabetes management in teens is fairly limited, with some initial support for improvements in both behavioral and clinical outcomes among teens. More research is clearly needed in order to further determine how gaming can best be utilized to impact health outcomes in these teens, as well as potential mechanisms of change. 相似文献
109.
Cytokinesis-blocked micronucleus cytome assay biomarkers identify lung cancer cases amongst smokers.
Randa A El-Zein Michael Fenech Mirtha S Lopez Margaret R Spitz Carol J Etzel 《Cancer epidemiology, biomarkers & prevention》2008,17(5):1111-1119
The multi-endpoint cytokinesis-blocked micronucleus assay is used for assessing chromosome aberrations. We have recently reported that this assay is extremely sensitive to genetic damage caused by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and that the binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds in lymphocytes (chromosome damage endpoints measured by the assay) are strong predictors of lung cancer risk. In the current study, we refined our analysis to include toxicity endpoints (micronuclei in mononucleated cells, apoptosis, necrosis, and nuclear division index) to investigate the benefit of including these variables on improving the predictive value of the assay. Baseline and NNK-induced micronuclei in mononucleated cells were significantly higher in patients (n = 139) than controls (n = 130; P < 0.001). Baseline apoptosis was higher among cases; however, the controls showed a significant higher fold increase in NNK-induced apoptosis compared with baseline (P < 0.001). Principal components analysis was used to derive a summary measure for all endpoints and calculate the positive predictive value (PPV) and negative predictive value (NPV) for disease status. First principal component for NNK-induced chromosome damage endpoints (binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds) had an area under the curve = 97.9 (95% confidence interval, 95.9-99.0), PPV = 94.8, and NPV = 92.6. The discriminatory power improved when micronuclei in mononucleated cells were included: area under the curve = 99.1 (95% confidence interval, 97.9-100.0), PPV = 98.7 and NPV = 95.6. The simplicity, rapidity, and sensitivity of the assay together with potential for automation make it a valuable tool for screening and prioritizing potential cases for intensive screening. 相似文献
110.
Talía Malagón Karena D. Volesky Sheila Bouten Claudie Laprise Mariam El-Zein Eduardo L. Franco 《International journal of cancer. Journal international du cancer》2020,147(10):2695-2707
Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen-management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta-analysis of progression rates to precancer and cancer for HPV-positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV-positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random-effects meta-regression model. We used the model to predict HPV type-specific risks of precancer and cancer over follow-up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high-risk HPV positive but cytology/histology normal women was 1.0 per 100 women-years (95% CI: 1.0-1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0-9.5), 4.3% (95% prediction interval 0.0-11.5) and 6.4% (95% prediction interval 0.0-13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P-value < .0001). Our HPV type-specific progression risk estimates can help inform risk-based cervical cancer screening guidelines for HPV-positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations. 相似文献