首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1406篇
  免费   101篇
  国内免费   1篇
  2022年   6篇
  2021年   24篇
  2020年   17篇
  2019年   18篇
  2018年   26篇
  2017年   19篇
  2016年   39篇
  2015年   67篇
  2014年   63篇
  2013年   88篇
  2012年   110篇
  2011年   77篇
  2010年   42篇
  2009年   50篇
  2008年   75篇
  2007年   67篇
  2006年   78篇
  2005年   53篇
  2004年   60篇
  2003年   49篇
  2002年   57篇
  2001年   10篇
  2000年   25篇
  1999年   22篇
  1998年   26篇
  1997年   18篇
  1996年   17篇
  1995年   23篇
  1994年   20篇
  1993年   13篇
  1992年   21篇
  1991年   15篇
  1990年   20篇
  1989年   11篇
  1988年   8篇
  1987年   9篇
  1986年   5篇
  1984年   7篇
  1983年   9篇
  1982年   10篇
  1981年   17篇
  1980年   7篇
  1979年   10篇
  1978年   8篇
  1977年   8篇
  1976年   10篇
  1975年   14篇
  1974年   8篇
  1973年   6篇
  1967年   6篇
排序方式: 共有1508条查询结果,搜索用时 402 毫秒
61.
62.

Background

Measurements of tumour metabolism by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) have been successfully applied to monitor tumour response after chemo- and chemo-radiotherapy and may not have the same limitations as other morphological imaging techniques. In this study it is investigated whether FDG-PET might add information on the efficacy of immune therapy.

Materials and methods

In a retrospective analysis data from patients with advanced progressive melanoma, treated with DC vaccinations and evaluated by PET/CT scans at baseline as well as after 6 vaccinations were analysed. If a patient achieved stable disease according to RECIST, additional vaccinations were given. The PET scans were evaluated according to EORTC guidelines.

Results

PET/CT scans from 13 patients were evaluated. According to RECIST 3 patients achieved stable disease and 10 patients progressed. Interestingly, when evaluated by PET scans 2 patients had partial metabolic response and 1 patient had complete metabolic response of the 2 index lesions even though a new lesion appeared simultaneously. Ten patients were seen to have stable or progressive metabolic disease.

Conclusion

By adding PET scans to the CT evaluation of patients treated with DC vaccines, a more detailed picture of the single lesions was found. This seems to improve the clinical evaluation of the treatment. The lack of correlation between the PET and CT scans suggests that some of the increases in target lesions seen in CT scans might be due to oedema or immune-infiltrates and not progression of the disease. Thus, further investigation into the contribution of PET scans to the evaluation of cancer immunotherapy is needed.  相似文献   
63.
GB virus C (GBV‐C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV‐positive patients. However, the prevalence of GBV‐C in HIV‐positive individuals in Indonesia is unknown. Since GBV‐C is more prevalent in anti‐HCV positive patients than in anti‐HCV negative subjects, transmission of GBV‐C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV‐C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV‐C among HIV patients (n = 125, median age 31 years) based on the 5′UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV‐infected patients with and without HCV infection, respectively. GBV‐C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co‐infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV‐C among HIV‐positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6.  相似文献   
64.
Abstract

A general strategy for performing energy minimization of proteins using the SYBYL molecular modelling program has been developed. The influence of several variables including energy minimization procedure, solvation, dielectric function and dielectric constant have been investigated in order to develop a general method, which is capable of producing high quality protein structures. Avian pancreatic polypeptide (APP) and bovine pancreatic phospholipase A2 (BP PLA2) were selected for the calculations, because high quality X-ray structures exist and because all classes of secondary structure are represented in the structures. The energy minimized structures were evaluated relative to the corresponding X-ray structures. The overall similarity was checked by calculating RMS distances for all atom positions. Backbone conformation was checked by Ramachandran plots and secondary structure elements evaluated by the length on hydrogen bonds. The dimensions of active site in BP PLA2 is very dependent on electrostatic interactions, due to the presence of the positively charged calcium ion. Thus, the distances between calcium and the calcium-coordinating groups were used as a quality index for this protein. Energy minimized structures of the trimeric PLA2 from Indian cobra (N.n.n. PLA2) were used for assessing the impact of protein-protein interactions. Based on the above mentioned criteria, it could be concluded that using the following conditions: Dielectric constant ? = 4 or 20; a distance dependent dielectric function and stepwise energy minimization, it is possible to reproduce X-ray structures very accurately without including explicit solvent molecules.  相似文献   
65.
Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low‐density lipoprotein (LDL)‐cholesterol were lower after the working period than after the week‐off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high‐density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week‐off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift‐working women. It was also shown that susceptible shift workers had worse lipid profiles.  相似文献   
66.
Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2PP2A, except when I2PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.  相似文献   
67.
68.
69.
Unhealthy dietary pattern increases the risk of obesity and metabolic disorders in growing children and adolescents. However, the way the habitual pattern of breakfast consumption influences body composition and risk of obesity in adolescents is not well defined. Thus, the aim of the present study was to assess any associations between breakfast consumption practices and body composition profiles in 236 apparently healthy adolescents aged 12 to 19 years. A self-administered questionnaire on dietary behaviour and lifestyle practices and a dietary food frequency questionnaire were used. Body composition and adiposity indices were determined using standard anthropometric measurement protocols and dual energy χ-ray absorptiometry (DXA). Mean age of the participants was 15.3±1.9 years. The majority of participants (71.2%) fell in the normal body mass index (BMI) ranges. Breakfast consumption patterns showed that only half of the participants (50%) were consuming breakfast daily. Gender-specific multivariate analyses (ANCOVA) showed that in both boys and girls, those eating breakfast at least 5 times a week had significantly lower body weight, body mass index (BMI), BMI z-scores, waist circumference, body fat mass and percent body fat (%BF) compared to infrequent breakfast eaters, after adjustment for age, household income, pubertal status, eating-out and snacking practices, daily energy intakes, and daily physical activity levels. The present findings indicate that infrequent breakfast consumption is associated with higher body adiposity and abdominal obesity. Therefore, daily breakfast consumption with healthy food choices should be encouraged in growing children and adolescents to prevent adiposity during these critical years of growth.  相似文献   
70.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号