全文获取类型
收费全文 | 2158篇 |
免费 | 213篇 |
国内免费 | 2篇 |
出版年
2023年 | 14篇 |
2022年 | 30篇 |
2021年 | 33篇 |
2020年 | 22篇 |
2019年 | 21篇 |
2018年 | 25篇 |
2017年 | 22篇 |
2016年 | 45篇 |
2015年 | 101篇 |
2014年 | 119篇 |
2013年 | 135篇 |
2012年 | 157篇 |
2011年 | 162篇 |
2010年 | 104篇 |
2009年 | 81篇 |
2008年 | 108篇 |
2007年 | 91篇 |
2006年 | 131篇 |
2005年 | 94篇 |
2004年 | 88篇 |
2003年 | 75篇 |
2002年 | 72篇 |
2001年 | 61篇 |
2000年 | 67篇 |
1999年 | 55篇 |
1998年 | 18篇 |
1997年 | 21篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 12篇 |
1992年 | 24篇 |
1991年 | 32篇 |
1990年 | 13篇 |
1989年 | 23篇 |
1988年 | 26篇 |
1987年 | 19篇 |
1986年 | 31篇 |
1985年 | 26篇 |
1984年 | 19篇 |
1983年 | 16篇 |
1982年 | 8篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1978年 | 15篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1973年 | 9篇 |
1969年 | 6篇 |
1966年 | 6篇 |
排序方式: 共有2373条查询结果,搜索用时 62 毫秒
81.
Chun-Ho Yun Hiram G. Bezerra Tung-Hsin Wu Fei-Shih Yang Chuan-Chuan Liu Yih-Jer Wu Jen-Yuan Kuo Chung-Lieh Hung Jason Jeun-Shenn Lee Charles Jia-Yin Hou Hung-I Yeh Chris T. Longenecker Ricardo C. Cury 《PloS one》2013,8(4)
Background
The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized.Materials and Methods
In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines.Results
TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05). Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05), serum insulin (ß-coef.:0.17, p<0.05) and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05). These relationships persisted after adjustment in multivariable models (all p<0.05). A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74–0.83) to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05).Conclusion
In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and subclinical atherosclerosis in a relatively healthy population. 相似文献82.
Li-Yu Hu Cheng-Che Shen Yu-Wen Hu Mu-Hong Chen Chia-Fen Tsai Huey-Ling Chiang Chiu-Mei Yeh Wei-Shu Wang Pan-Ming Chen Tsung-Ming Hu Tzeng-Ji Chen Tung-Ping Su Chia-Jen Liu 《PloS one》2013,8(8)
Background
Thyroid disorders have long been associated with psychiatric illness, often with symptoms suggestive of mood disorders. The most common clinical features associated with hyperthyroidism are anxiety and depression. The risk of bipolar disorders, especially bipolar mania, among patients with thyroid disorders has not been well characterized.Objective
We explored the relationship of hyperthyroidism and the subsequent development of bipolar disorders, and examined the risk factors for bipolar disorders in patients with hyperthyroidism.Methods
We identified patients who were diagnosed with hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort without hyperthyroidism was matched based on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated in both cohorts based on diagnosis and the use of mood stabilizer drugs.Results
The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison cohort consisted of 21, 574 matched control patients without hyperthyroidism. The incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80–2.99, P<.001) was higher for the hyperthyroidism patients than the control patients. Multivariate, matched regression models showed that women (HR 2.02, 95% CI 1.34–3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI 1.58–5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18–2.43, P = .004) were independent risk factors for the development of bipolar disorders in hyperthyroidism patients.Conclusions
Although a possibility that the diagnosis of bipolar disorders in this study actually includes "bipolar disorders due to hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may increase the risk of developing bipolar disorders. 相似文献83.
Hui-Wen Chiu Ya-Ling Yeh Yi-Ching Wang Wei-Jan Huang Yi-An Chen Yi-Shiou Chiou Sheng-Yow Ho Pinpin Lin Ying-Jan Wang 《PloS one》2013,8(10)
Triple-negative breast cancer (TNBC), defined by the absence of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, is associated with an early recurrence of disease and poor outcome. Furthermore, the majority of deaths in breast cancer patients are from metastases instead of from primary tumors. In this study, MCF-7 (an estrogen receptor-positive human breast cancer cell line), MDA-MB-231 (a human TNBC cell line) and 4T1 (a mouse TNBC cell line) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with suberoylanilide hydroxamic acid (SAHA, an inhibitor of histone deacetylase (HDAC)) and to determine the underlying mechanisms of these effects in vitro and in vivo. We also evaluated the ability of SAHA to inhibit the metastasis of 4T1 cells. We found that IR combined with SAHA showed increased therapeutic efficacy when compared with either treatment alone in MCF-7, MDA-MB-231 and 4T1 cells. Moreover, the combined treatment enhanced DNA damage through the inhibition of DNA repair proteins. The combined treatment was induced primarily through autophagy and ER stress. In an orthotopic breast cancer mouse model, the combination treatment showed a greater inhibition of tumor growth. In addition, SAHA inhibited the migration and invasion abilities of 4T1 cells and inhibited breast cancer cell migration by inhibiting the activity of MMP-9. In an in vivo experimental metastasis mouse model, SAHA significantly inhibited lung metastasis. SAHA not only enhances radiosensitivity but also suppresses lung metastasis in breast cancer. These novel findings suggest that SAHA alone or combined with IR could serve as a potential therapeutic strategy for breast cancer. 相似文献
84.
Atomic force microscopy provides a novel technique for differentiating the mechanical properties of various cell types. Cell elasticity is abundantly used to represent the structural strength of cells in different conditions. In this study, we are interested in whether physical or physiological cues affect cell elasticity in Atomic force microscopy (AFM)-based assessments. The physical cues include the geometry of the AFM tips, the indenting force and the operating temperature of the AFM. All of these cues show a significant influence on the cell elasticity assessment. Sharp AFM tips create a two-fold increase in the value of the effective Young’s modulus (Eeff) relative to that of the blunt tips. Higher indenting force at the same loading rate generates higher estimated cell elasticity. Increasing the operation temperature of the AFM leads to decreases in the cell stiffness because the structure of actin filaments becomes disorganized. The physiological cues include the presence of fetal bovine serum or extracellular matrix-coated surfaces, the culture passage number, and the culture density. Both fetal bovine serum and the extracellular matrix are critical for cells to maintain the integrity of actin filaments and consequently exhibit higher elasticity. Unlike primary cells, mouse kidney progenitor cells can be passaged and maintain their morphology and elasticity for a very long period without a senescence phenotype. Finally, cell elasticity increases with increasing culture density only in MDCK epithelial cells. In summary, for researchers who use AFM to assess cell elasticity, our results provide basic and significant information about the suitable selection of physical and physiological cues. 相似文献
85.
86.
Li Liu T. Kevin Hitchens Qing Ye Yijen Wu Brent Barbe Devin E. Prior Wendy F. Li Fang-Cheng Yeh Lesley M. Foley Daniel J. Bain Chien Ho 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency.Methods
Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2 g/kg) 1 h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology.Results
Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60 pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48 h for USPIO and MPIO, respectively.Conclusions
Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles.General significance
Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver. 相似文献87.
88.
Background and objective
The genetic variants of xenobiotic-metabolizing enzymes, such as those encoded by glutathione-S-transferase (GST) genes, may be associated with the risk of coronary artery disease (CAD). To investigate the genetic factors for CAD, we examined the GSTM1, GSTT1, GSTP1, and GSTA1 genotypes in a CAD cohort in Taiwan.Methods
Our study included 458 CAD participants and 209 control participants who received coronary angiography to assess CAD. The severity of CAD was defined as the number of coronary vessels with 50% or greater stenosis. Sequence variation of the GSTM1 and GSTT1 genes was determined using a polymerase chain reaction (PCR). The GSTP1 (Ile105Val), and GSTA1 (-69C > T) genetic variants were identified using a combination of PCR and restriction fragment length polymorphism analysis. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals.Results
Among the GST genetic variants examined, the GSTT1 null genotype was more prevalent in CAD participants with 3 stenosed vessels than in control participants (OR = 1.64, P = .02). This association was no longer observed after adjusting for age, sex, smoking, alcohol use, diabetes mellitus, and serum levels of total cholesterol and high-density lipoprotein cholesterol (OR = 1.28, P = .40). Both univariate and multivariate logistic regression analyses found no significant associations between CAD and the other genetic variants, either separately or in combination. In addition, no effects of interactions between the genotypes and environmental factors, such as cigarette smoking, were significantly associated with the risk of CAD.Conclusion
The GST genetic variants examined were not associated with susceptibility to CAD in our Taiwanese cohort. This null association requires further confirmation with larger samples. 相似文献89.
Dah-Yuu Lu Bor-Ren Huang Wei-Lan Yeh Hsiao-Yun Lin Shiang-Suo Huang Yu-Shu Liu Yueh-Hsiung Kuo 《Molecular neurobiology》2013,48(3):863-874
Accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in several neurodegenerative disorders. Therefore, development of methods for microglial inhibition is considered an important strategy in the search for neuroprotective agents. Caffeic acid phenethyl ester (CAPE) is distributed wildly in nature, but rapid decomposition by esterase leads to its low bioavailability. In this study, we investigated the effects of KS370G, a novel caffeic acid phenylethyl amide, on microglial activation. KS370G significantly inhibited the release of nitric oxide (NO) and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with KS370G also induced heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS)-3 expression in the microglia. Furthermore, the anti-inflammatory effects of KS370G were found to be regulated by phosphorylated adenosine monophosphate-activated protein kinase-α (AMPK-α) translocated to the nucleus. Moreover, KS370G showed significant anti-neuroinflammatory effects on microglial activation in vivo and on motor behavior as well. The protective effect of KS370G was weakened by an AMPK inhibitor Compound C. This study focuses on the importance of key molecular determinants of inflammatory homeostasis, AMPK, HO-1, and SOCS-3, and their possible involvement in anti-neuroinflammatory responses. 相似文献
90.