全文获取类型
收费全文 | 374篇 |
免费 | 24篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 19篇 |
妇产科学 | 6篇 |
基础医学 | 35篇 |
口腔科学 | 13篇 |
临床医学 | 21篇 |
内科学 | 88篇 |
皮肤病学 | 7篇 |
神经病学 | 21篇 |
特种医学 | 6篇 |
外科学 | 39篇 |
综合类 | 10篇 |
预防医学 | 46篇 |
眼科学 | 4篇 |
药学 | 25篇 |
中国医学 | 2篇 |
肿瘤学 | 52篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 14篇 |
2020年 | 6篇 |
2019年 | 13篇 |
2018年 | 16篇 |
2017年 | 20篇 |
2016年 | 19篇 |
2015年 | 9篇 |
2014年 | 27篇 |
2013年 | 37篇 |
2012年 | 38篇 |
2011年 | 33篇 |
2010年 | 27篇 |
2009年 | 16篇 |
2008年 | 21篇 |
2007年 | 25篇 |
2006年 | 6篇 |
2005年 | 11篇 |
2004年 | 9篇 |
2003年 | 15篇 |
2002年 | 16篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有401条查询结果,搜索用时 15 毫秒
31.
Ivo Veletic Sanja Prijic Taghi Manshouri Graciela M. Nogueras-Gonzalez Srdan Verstovsek Zeev Estrov 《Haematologica》2021,106(9):2384
Phenotypic characterization of T cells in myelofibrosis is intriguing because of increased inflammation, markedly elevated pro-inflammatory cytokines, and altered distribution of T-cell subsets. Constitutive activation of Janus kinase-2 (JAK2) in the majority of patients with myelofibrosis contributes to the expression of the programmed cell death protein-1 (PD1) and T-cell exhaustion. We wondered whether T-cell activation affects treatment outcome of patients with myelofibrosis and sought to determine whether the JAK1/2 inhibitor ruxolitinib affects the activation of T-cell subsets. T cells from 47 myelofibrosis patients were analyzed and the percentages of either helper (CD4+) or cytotoxic (CD8+) naïve, central memory, effector memory, or effector T cells; and fractions of PD1-expressing cells in each subset were assessed. Higher numbers of T cells co-expressing CD4/PD1 and CD8/PD1 were found in myelofibrosis patients than in healthy controls (n=28), and the T cells were significantly skewed toward an effector phenotype in both CD4+ and CD8+ subsets, consistent with a shift from a quiescent to an activated state. Over the course of ruxolitinib treatment, the distribution of aberrant T-cell subsets significantly reversed towards resting cell phenotypes. CD4+ and CD8+ subsets at baseline correlated with monocyte and platelet counts, and their PD1+ fractions correlated with leukocyte counts and spleen size. Low numbers of PD1+/CD4+ and PD1+/CD8+ cells were associated with complete resolution of palpable splenomegaly and improved survival rate, suggesting that low levels of exhausted T cells confer a favorable response to ruxolitinib treatment. 相似文献
32.
Raeisossadati R Farshchian M Ganji A Tavassoli A Velayati A Dadkhah E Chavoshi S Mehrabi Bahar M Memar B Rajabi Mashhadi MT Naseh H Forghanifard MM Moghbeli M Moaven O Abbaszadegan MR 《International journal of colorectal disease》2011,26(10):1265-1270
Background
Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.Methods
A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.Results
TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.Conclusions
TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread. 相似文献33.
Warren Fiskus Christopher P. Mill Behnam Nabet Dimuthu Perera Christine Birdwell Taghi Manshouri Bernardo Lara Tapan M. Kadia Courtney DiNardo Koichi Takahashi Naval Daver Prithviraj Bose Lucia Masarova Naveen Pemmaraju Steven Kornblau Gautam Borthakur Guillermo Montalban-Bravo Guillermo Garcia Manero Sunil Sharma Matthew Stubbs Xiaoping Su Michael R. Green Cristian Coarfa Srdan Verstovsek Joseph D. Khoury Christopher R. Vakoc Kapil N. Bhalla 《Blood cancer journal》2021,11(5)
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies 相似文献
34.
Amiri I Karimi J Piri H Goodarzi MT Tavilani H Khodadadi I Ghorbani M 《Systems biology in reproductive medicine》2011,57(6):292-295
The incidence of diabetes mellitus is rapidly increasing in the world. One of the complications of diabetes includes disturbance of the reproductive tract, such as infertility, erectile dysfunction, and endocrine disruption. Nitric oxide (NO) is a free radical produced by most cells including the human male and female reproductive tracts. NO has a dual role where low concentrations are essential for homeostatic cellular biology and physiology, but high levels have detrimental effects relating to cellular damage from this reactive oxygen species (ROS). 8-hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside of DNA that is currently used as a biomarker of cellular oxidative stress, where urinary levels can correlate with diabetic nephropathy and retinopathy. Our aim was to investigate the relationship between nitrate/nitrite levels and 8-OHdG levels in the semen of diabetic and non-diabetic men. Concentrations of nitrate/nitrite and 8-OHdG were examined in seminal plasma of 32 diabetic and 35 non-diabetic men. The level of nitrate/nitrite was assayed by colorimetric reaction and 8-OHdG was measured by ELISA. Our results showed that the seminal plasma nitrate/nitrite levels were significantly higher in the diabetic group (p?0. 01). There were also significantly higher 8-OHdG levels in diabetic men compared to non-diabetic men (p?0.05). Regression analysis indicated that in diabetic men, nitrate/nitrite levels correlated well with 8-OHdG levels (r?=?0.64, p?0.001). A significant trend between nitrate/nitrite and sperm parameters was not observed. Our data suggests that high levels of nitrate/nitrite in the semen of diabetic men is suggestive of reactive oxygen species induced DNA damage that is correlated with 8-OHdG levels but not sperm parameters. These results support the further investigation of NO and 8-OHdG as biomarkers for assessing male infertility. 相似文献
35.
Ramezani A Goudarzi I Lashkarbolouki T Ghorbanian MT Salmani ME Abrari K 《Pharmacology, biochemistry, and behavior》2011,100(1):144-151
During particular periods of central nervous system (CNS) development, exposure to ethanol can decrease regional brain growth and can result in selective loss of neurons. Unfortunately, there are few effective means of attenuating damage in the immature brain. In this study, the possible antioxidant and neuroprotective properties of 17β-estradiol against ethanol-induced neurotoxicity was investigated. 17β-estradiol (600 μg/kg) was injected subcutaneously in postnatal day (PD) 4 and 5, 30 min prior to intraperitoneal injection of ethanol (6 g/kg) in rat pups. Ninety minutes after injection of ethanol, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substance (TBARS) levels were also measured as a marker of lipid peroxidation. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral measurements in postnatal day 23. The results of the present work demonstrated that ethanol could induce lipid peroxidation, increase TBARS levels and decrease glutathione peroxidase levels in pup cerebellum. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rat pups. However, treatment with 17β-estradiol significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidants. Histological analysis also indicated that ethanol could decrease vermis Purkinje cell count and 17β-estradiol prevented this toxic effect. These results suggest that ethanol may induce lipid peroxidation in the rat pups cerebellum while treatment with 17β-estradiol improves motor deficits by protecting the cerebellum against ethanol toxicity. 相似文献
36.
37.
38.
Khotaei GT Jam S SeyedAlinaghi S Motamed F Nejat F Taghi M Ashtiani H Izadyar M 《Acta medica Iranica》2010,48(2):91-94
Vancomycin is a a glycopeptide antibiotic with bacetiocidal effects on gram positive bacteria by interfering with cell wall synthesis. The necessity for monitoring of serum vancomycin concentrations (SVCs) has been recently noticed at many institutions because of concerns for its nephrotoxicity. We aimed to describe the SVCs monitoring in pediatric patients, in an effort to determine subtherapeutic or toxic levels. The medical records were reviewed for all patients older than 60 days of age admitted to the general or subspecialty services who received intravenous vancomycin at Children's Medical Hospital in Tehran, Iran between July 2003 and December 2005. Because pharmacokinetic parameters for children with cancer may be different, this group was evaluated separately. During the study, 167 infants and children without cancer and 42 patients with cancer; aged between 3 months to 17.5 years were treated with vancomycin for various infections. In children without cancer, peak SVCs were in an adequate therapeutic range for 93% of patients (8-55 microg/ml). For children with cancer, peak SVCs was lower than 10 microg/ml (10%), and trough values were lower than 5 microg/ml (21%). In conclusion, according to the results of this research, due to different pharmacokinetics of vancomycin in cancerous patients, the monitoring of vancomycin plasma concentrations is necessary for the best therapeutic antibacterial activities with a fewer occurrence of serious adverse effects. 相似文献
39.
Sareh Keshavarzi Seyyed Mohammad Taghi Ayatollahi Najaf Zare Farkhondeh Sharif 《Quality of life research》2013,22(6):1255-1263
Purpose
This article is a report of using seemingly unrelated regression (SUR) models to examine the determinants of different dimensions of quality of life (QoL) among childbearing age women. There are a limited number of studies on QoL and its associated factors among women in developing countries such as Iran. Therefore, more attention should be focused on identifying these issues.Methods
We administered the Persian’s abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire to 1,067 married women aged between 15 and 49 years. The women were chosen via a multistage research design from the rural region of Shiraz, the center of Fars Province in Iran in 2008. Clinical and socio-demographic characteristics as well as their reproductive health-related characteristics were investigated. To identify associated factors of QoL dimensions, ordinary least squares (OLS) regression and SUR were used and their findings were compared.Results
The WHOQOL-BREF showed acceptable consistency (Cronbach’s alpha range: 0.62–0.75 across domains). Lower age, absence of long-term illness, economic status satisfaction, higher level of education, lower number of pregnancies, and higher body mass index were important associated factors of different dimensions of the QoL among these women. The estimated parameters for these factors were in close agreement in both OLS and SUR estimation methods. However, the SUR estimator provided the higher precision of the estimates than the OLS estimator, as the parameters obtained by SUR are characterized by lower standard errors. Women’s age, income satisfaction, and level of education were common for all domains.Conclusions
This study presents a novel approach to simultaneously predict QoL domains using the SUR estimators and the results are relevant for implementing objective QoL. SUR estimators performed consistently better than the OLS estimators, since SUR takes the correlation between error terms into account. Thus, the SUR method could be a useful methodology for predicting QoL domains. 相似文献40.
Mehrdad Roghani Mohammad‐Reza Vaez Mahdavi Mohammad‐Reza Jalali‐Nadoushan Tourandokht Baluchnejadmojarad Gholamali Naderi Farshad Roghani‐Dehkordi Mohammad Taghi Joghataei Maryam Kord 《Phytotherapy research : PTR》2013,27(1):112-117
The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin‐diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium‐intact rings to PE was significantly lower in daidzein‐treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium‐dependent relaxation to ACh was significantly higher in daidzein‐treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)‐nitro‐l‐arginine methyl ester and/or indomethacin attenuated it. Two‐month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin‐related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献