全文获取类型
收费全文 | 2006篇 |
免费 | 170篇 |
国内免费 | 2篇 |
专业分类
2178篇 |
出版年
2022年 | 18篇 |
2021年 | 27篇 |
2020年 | 18篇 |
2019年 | 21篇 |
2018年 | 21篇 |
2017年 | 28篇 |
2016年 | 57篇 |
2015年 | 98篇 |
2014年 | 102篇 |
2013年 | 146篇 |
2012年 | 164篇 |
2011年 | 145篇 |
2010年 | 101篇 |
2009年 | 81篇 |
2008年 | 112篇 |
2007年 | 88篇 |
2006年 | 82篇 |
2005年 | 77篇 |
2004年 | 79篇 |
2003年 | 66篇 |
2002年 | 56篇 |
2001年 | 55篇 |
2000年 | 50篇 |
1999年 | 37篇 |
1998年 | 21篇 |
1997年 | 21篇 |
1996年 | 26篇 |
1995年 | 11篇 |
1994年 | 24篇 |
1993年 | 12篇 |
1992年 | 24篇 |
1991年 | 28篇 |
1990年 | 19篇 |
1989年 | 12篇 |
1988年 | 18篇 |
1987年 | 17篇 |
1986年 | 17篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 16篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 11篇 |
1979年 | 20篇 |
1978年 | 10篇 |
1976年 | 19篇 |
1975年 | 12篇 |
1974年 | 6篇 |
1973年 | 8篇 |
1970年 | 8篇 |
排序方式: 共有2178条查询结果,搜索用时 15 毫秒
71.
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72.
Kuo-How Huang Kuan-Lin Kuo I-Lin Ho Hong-Chiang Chang Yuan-Ting Chuang Wei-Chou Lin Ping-Yi Lee Shih-Chen Chang Chih-Kang Chiang Yeong-Shiau Pu Chien-Tso Chou Chen-Hsun Hsu Shing-Hwa Liu 《PloS one》2013,8(12)
Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC. 相似文献
73.
AbstractBiodegradable polymers are promising binders and carriers for natural antifoulants. In the present study, an antifouling (AF) coating was developed by adding a non-toxic AF compound (butenolide) to a bio-based and biodegradable poly(lactic acid)-based polyurethane. Mass loss measurement showed that the polymer degraded in seawater at a rate of 0.013?mg cm?2?day?1. Measurements showed that butenolide was released from the coatings into seawater over a period of at least three months. Both the concentration of butenolide in the coatings and the ambient temperature determined the release rate of butenolide. The results further demonstrate that incorporating rosin into the coatings increase the self-renewal rate of the polymer and facilitated the long-term release of butenolide from the coating. The results show that poly(lactic acid)-based polyurethane is a suitable polymer for butenolide-based AF coatings. 相似文献
74.
Nilüfer N. Turan Karni S. Moshal Karim Roder Brett C. Baggett Anatoli Y. Kabakov Saroj Dhakal Ryota Teramoto David Yi-Eng Chiang Mingwang Zhong An Xie Yichun Lu Samuel C. Dudley Jr. Calum A. MacRae Alain Karma Gideon Koren 《The Journal of biological chemistry》2020,295(52):18148
The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation. 相似文献
75.
This work presents the Protein Association Analyzer (PRASA) (http://zoro.ee.ncku.edu.tw/prasa/) that predicts protein interactions as well as interaction types. Protein interactions are essential to most biological functions. The existence of diverse interaction types, such as physically contacted or functionally related interactions, makes protein interactions complex. Different interaction types are distinct and should not be confused. However, most existing tools focus on a specific interaction type or mix different interaction types. This work collected 7234058 associations with experimentally verified interaction types from five databases and compiled individual probabilistic models for different interaction types. The PRASA result page shows predicted associations and their related references by interaction type. Experimental results demonstrate the performance difference when distinguishing between different interaction types. The PRASA provides a centralized and organized platform for easy browsing, downloading and comparing of interaction types, which helps reveal insights into the complex roles that proteins play in organisms. 相似文献
76.
77.
78.
Asheesh Gupta Pinar Avci Magesh Sadasivam Rakkiyappan Chandran Nivaldo Parizotto Daniela Vecchio Wanessa C.M.A. de Melo Tianhong Dai Long Y. Chiang Michael R. Hamblin 《Biotechnology advances》2013
Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. 相似文献
79.
80.
Alfred N. Fonteh Jiarong Chiang Matthew Cipolla Jack Hale Fatimatou Diallo Alejandra Chirino Xianghong Arakaki Michael G. Harrington 《Journal of lipid research》2013,54(10):2884-2897
Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer''s disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. 相似文献