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Maternal Multivitamin Intake,Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring 下载免费PDF全文
Ramkripa Raghavan Anne W. Riley Heather Volk Deanna Caruso Lynn Hironaka Laura Sices Xiumei Hong Guoying Wang Yuelong Ji Martha Brucato Anastacia Wahl Tom Stivers Colleen Pearson Barry Zuckerman Elizabeth A. Stuart Rebecca Landa M. Daniele Fallin Xiaobin Wang 《Paediatric and perinatal epidemiology》2018,32(1):100-111
Background
To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk.Methods
This report included 1257 mother–child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2–3 days after birth.Results
Moderate (3–5 times/week) self‐reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5).Conclusion
There was a ‘U shaped’ relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis‐generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in‐utero on early brain development. 相似文献3.
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Twenty-three cases of basaloid squamous cell carcinoma (BSCC) and 23 stage-matched pairs of typical squamous cell carcinoma (SCC) of the oesophagus were investigated for molecular aberrations. Polymerase chain reaction (PCR) was used to detect loss of heterozygosity at the APC, RB, and MCC gene loci, while differential PCR was carried out to detect amplification of the CDK4 gene. In addition, the level of expression of the p53 and RB proteins in the tumour tissue was assessed by immunohistochemistry. Loss of heterozygosity (LOH) at the APC and MCC loci was about twice as common in BSCC as in SCC (40% vs. 21% and 33% vs. 12%, respectively), with co-existence of LOH at both loci occurring only in BSCC. LOH frequency at the RB gene locus was not remarkably different in either BSCC or SCC (20% vs. 24%, respectively). On immunohistochemistry, accumulation of p53 protein was slightly more frequent in BSCC than in SCC (61% vs. 52%), whereas the rate of loss of RB protein expression was about equal in both types of carcinoma (9% vs. 13% BSCC and SCC, respectively). There was no detectable amplification of the CDK4 gene in either type of tumour. Although the observed differences did not achieve statistical significance, this work has further highlighted possible differences between the molecular pathogenesis of BSCC and SCC. 相似文献
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Elissa M. Ozanne PhD rea Loberg Sherwood Hughes Christine Lawrence Brian Drohan MS Alan Semine MD Michael Jellinek MD Claire Cronin MD Frederick Milham MD MBA Dana Dowd RN NP Caroline Block MD Deborah Lockhart John Sharko MS Georges Grinstein PhD Kevin S. Hughes MD 《The breast journal》2009,15(2):155-162
Abstract: Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective. 相似文献
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Jennie M. Kuckertz Nader Amir Anastacia C. Tobin Sadia Najmi 《Cognitive therapy and research》2013,37(2):232-241
In two experiments we examined the psychometric properties of a new measure of interpretation bias in individuals with obsessive-compulsive symptoms (OCs). In Experiment 1, 38 individuals high in OC symptoms, 34 individuals high in anxiety and dysphoric symptoms, and 31 asymptomatic individuals completed the measure. Results revealed that the Word Sentence Association Test for OCD (WSAO) can differentiate those with OC symptoms from both a matched anxious/dysphoric group and a non-anxious/non-dysphoric group. In a second experiment, we tested the predictive validity of the WSAO using a performance-based behavioral approach test of contamination fears, and found that the WSAO was a better predictor of avoidance than an established measure of OC washing symptoms (Obsessive Compulsive Inventory-Revised, washing subscale). Our results provide preliminary evidence for the reliability and validity of the WSAO as well as its usefulness in predicting response to behavioral challenge above and beyond OC symptoms, depression, and anxiety. 相似文献
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Prostate epithelial cell growth is dependent on the presence of androgens, and transition of prostate cancer to an androgen-independent phenotype results in a highly aggressive, currently incurable cancer. We have developed a new preclinical model of androgen-independent prostate cancer derived from the VCaP prostate cancer epithelial cell line. VCaP cells were subcutaneously implanted and serially passaged in castrated male severe combined immunodeficient mice. Androgen independence was confirmed by WST-1 (a tetrazolium salt) cell proliferation assay in the absence or presence of dihydrotesterone (1-100 nM). VCaP androgen-sensitive cells responded dose dependently to dihydrotesterone, whereas VCaP androgen-independent cells did not alter their proliferation in response to dihydrotesterone. Gene expression of androgen receptor, B-cell lymphoma-2, prostate cancer antigen 3, prostate acid phosphatase, 6 transmembrane epithelial antigen of the prostate, and survivin was determined by polymerase chain reaction amplification. B-cell lymphoma-2 expression was up regulated in the VCaP androgen-independent lines compared to the VCaP androgen-sensitive, suggesting a possible mechanism of androgen independence. Furthermore, tumor-associated angiogenesis was assessed by immunofluorescence confocal microscopy of CD31. VCaP androgen-independent tumors showed enhanced angiogenesis compared to VCaP androgen-sensitive tumors. These results illustrate the development of a novel model of prostate cancer androgen independence and provide a new system to study angiogenesis and the transition to androgen independence. 相似文献