全文获取类型
收费全文 | 23745篇 |
免费 | 1621篇 |
国内免费 | 403篇 |
学科分类
医药卫生 | 25769篇 |
出版年
2024年 | 8篇 |
2023年 | 139篇 |
2022年 | 287篇 |
2021年 | 1155篇 |
2020年 | 516篇 |
2019年 | 734篇 |
2018年 | 862篇 |
2017年 | 694篇 |
2016年 | 1004篇 |
2015年 | 1310篇 |
2014年 | 1604篇 |
2013年 | 1713篇 |
2012年 | 2482篇 |
2011年 | 2386篇 |
2010年 | 1379篇 |
2009年 | 1054篇 |
2008年 | 1399篇 |
2007年 | 1388篇 |
2006年 | 1111篇 |
2005年 | 1055篇 |
2004年 | 838篇 |
2003年 | 688篇 |
2002年 | 541篇 |
2001年 | 339篇 |
2000年 | 309篇 |
1999年 | 211篇 |
1998年 | 105篇 |
1997年 | 76篇 |
1996年 | 44篇 |
1995年 | 32篇 |
1994年 | 34篇 |
1993年 | 23篇 |
1992年 | 48篇 |
1991年 | 32篇 |
1990年 | 36篇 |
1989年 | 24篇 |
1988年 | 22篇 |
1987年 | 12篇 |
1986年 | 18篇 |
1985年 | 16篇 |
1984年 | 5篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1976年 | 6篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1939年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Bo Mi Song Yumie Rhee Chang Oh Kim Yoosik Youm Kyoung Min Kim Eun Young Lee Ju-Mi Lee Young Mi Yoon Hyeon Chang Kim 《Nutrients》2014,6(12):5806-5818
An increasing number of studies report associations between low serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance; however, whether low vitamin D levels directly contribute to increased insulin resistance is unclear. We investigated the impact of residential area on the association between 25(OH)D and insulin resistance in elderly Koreans. Using data from the Korean Urban Rural Elderly study, we conducted cross-sectional analyses in 1628 participants (505 men and 1123 women). Serum 25(OH)D was analyzed as both continuous and categorized variables. Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using fasting blood glucose and insulin levels. In men, 25(OH)D level was inversely associated with HOMA-IR (standardized β = −0.133, p < 0.001) after adjustment for age, body mass index, waist circumference, smoking, alcohol intake, exercise, and study year. However, we noted significant urban-rural differences in 25(OH)D level (43.4 versus 65.6 nmol/L; p < 0.001) and HOMA-IR (1.2 versus 0.8 mmol·pmol/L2; p < 0.001). When we additionally adjusted for residential area, the association between 25(OH)D and HOMA-IR was attenuated (standardized β = −0.063, p = 0.115). In women, the association between 25(OH)D and HOMA-IR was not significant before or after adjustment for residential area. Environmental or lifestyle differences in urban and rural areas may largely explain the inverse association between serum 25(OH)D and insulin resistance. 相似文献
993.
Jung Ok Ban Dae Hwan Kim Hee Pom Lee Chul Ju Hwang Jung-Hyun Shim Dae Joong Kim Tae Myoung Kim Heon-Sang Jeong Seong Su Nah Hanyong Chen Zigang Dong Young Wan Ham Youngsoo Kim Sang-Bae Han Jin Tae Hong 《British journal of pharmacology》2014,171(11):2900-2912
Background and Purpose
Products of Maillard reactions between aminoacids and reducing sugars are known to have anti-inflammatory properties. Here we have assessed the anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its possible mechanisms of action.Experimental Approach
We used cultures of LPS-activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen-induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a pull-down assay and its binding site was predicted using molecular docking studies with Autodock VINA.Key Results
(E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5–10 μg·mL−1) inhibited LPS-inducedNO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen-induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull-down assay showed that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal bound to the DNA-binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner.Conclusions and Implications
(E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted anti-inflammatory and anti-arthritic effects through inhibition of the NF-κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease. 相似文献994.
995.
In Kyung Yoon Yun Jung Choi Byung Chul Chang Kyung Eun Lee Jeong Yeon Rhie Byung Koo Lee Hye Sun Gwak 《Archives of pharmacal research》2014,37(6):752-759
Cytokines that are involved in inflammation are related to blood coagulation, which could indirectly affect warfarin dose requirements. This study aimed to examine the effects of inflammatory cytokine gene polymorphisms on warfarin dose requirements for Korean patients with mechanical heart valves. In total, 191 patients with mechanical heart valves who were on warfarin anticoagulation therapy and maintained INR levels of 2–3 for three consecutive occasions were retrospectively followed up. In addition to vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 (CYP) 2C9 polymorphisms, the interferon-γ, interleukin-1β (IL1B), interleukin-6, interleukin-10, transforming growth factor-β1 (TGFB1), tumor necrosis factor-α, and C-reactive protein genotypes were determined. The predictive contribution of age, VKORC1, and CYP2C9 to variability was 46.0 %. The addition of IL1B and TGFB1 polymorphisms increased the R 2 to 48.8 % for stable dose requirements, and significantly higher doses were found, especially when the TGFB1 CC genotype was combined with the IL1B TT genotype. Based on the results, it was concluded that inflammatory cytokine genes, such as TGFB1 and IL1B, can be predictive variables for stable warfarin doses in Korean patients. 相似文献
996.
997.
998.
Min Song Jae Yun Hwang Min Young Lee Jun-Goo Jee You Mie Lee Jong-Sup Bae Jeong Ah Kim Seung Ho Lee Sangkyu Lee 《Archives of pharmacal research》2014,37(8):1063-1068
Piperlonguminine (PL), a major alkaloid isolated from Piper longum fruits, shows several biological activities including anti-tumor, anti-hyperlipidemic and anti-inflammatory effects. Although there have been studies of the biological effects of PL, the potential drug-interaction effect of PL following evaluation of inhibitory effects of cytochrome P450 (CYP) activities was not investigated. Here, to investigate the inhibitory effects of PL on the activities of CYP isoforms, CYP inhibition assays were conducted using a cocktail of probe substrates in pooled human liver microsome (HLMs) and human recombinant cDNA-expressed CYP. PL strongly inhibited CYP1A2-mediated phenacetin O-deethylation with an IC50 value of 8.8 μM, as NADPH-independent inhibition, while other CYPs were not significantly inhibited. A Lineweaver–Burk plot resulted in the inhibition mechanism of PL being divided into two different modes, reversible competitive inhibition in a low concentration range of 0–16 μM with a Ki value of 1.39 μM and uncompetitive inhibitory behavior at a high concentration range of 16–40 μM. In addition, PL only decreased CYP 1A2-catalyzed phenacetin O-deethylase activity with IC50 values of 10.0 μM in human recombinant cDNA-expressed 1A2, not 1A1. Overall, this is the first investigation of potential herb–drug interactions associated with PL conducted by identifying the competitive inhibitory effects of PL on CYP1A2 in HLMs. 相似文献
999.
Sun-A. Cho Yun Hyeok Jeong Ji Hoon Kim Seoyoung Kim Jun-Cheol Cho Young Heo Kyung-Do Suh Susun An Kyeho Shin 《Toxicology letters》2014
Cosmetics are normally composed of various ingredients. Some cosmetic ingredients can act as chemical haptens reacting toward proteins or peptides of human skin and they can provoke an immunologic reaction, called as skin sensitization. This haptenation process is very important step of inducing skin sensitization and evaluating the sensitizing potentials of cosmetic ingredients is very important for consumer safety. Therefore, animal alternative methods focusing on monitoring haptenation potential are undergoing vigorous research. To examine the further usefulness of spectrophotometric methods to monitor reactivity of chemicals toward peptides for cosmetic ingredients. Forty chemicals (25 sensitizers and 15 non-sensitizers) were reacted with 2 synthetic peptides, e.g., the cysteine peptides (Ac-RFAACAA-COOH) with free thiol group and the lysine peptides (Ac-RFAAKAA-COOH) with free amine group. Unreacted peptides can be detected after incubating with 5,5′-dithiobis-2-nitrobenzoic acid or fluorescamine™ as detection reagents for free thiol and amine group, respectively. Chemicals were categorized as sensitizers when they induced more than 10% depletion of cysteine peptides or more than 30% depletion of lysine peptides. The sensitivity, specificity, and accuracy were 80.0%, 86.7% and 82.5%, respectively. These results demonstrate that spectrophotometric methods can be an easy, fast, and high-throughput screening tools predicting the skin sensitization potential of chemical including cosmetic ingredient. 相似文献
1000.