全文获取类型
收费全文 | 403篇 |
免费 | 153篇 |
专业分类
儿科学 | 2篇 |
基础医学 | 20篇 |
临床医学 | 17篇 |
内科学 | 284篇 |
神经病学 | 18篇 |
外科学 | 10篇 |
综合类 | 18篇 |
预防医学 | 21篇 |
药学 | 148篇 |
中国医学 | 17篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 6篇 |
2021年 | 13篇 |
2020年 | 16篇 |
2019年 | 27篇 |
2018年 | 55篇 |
2017年 | 63篇 |
2016年 | 49篇 |
2015年 | 13篇 |
2014年 | 38篇 |
2013年 | 36篇 |
2012年 | 44篇 |
2011年 | 63篇 |
2010年 | 22篇 |
2009年 | 18篇 |
2008年 | 22篇 |
2007年 | 19篇 |
2006年 | 13篇 |
2005年 | 10篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有556条查询结果,搜索用时 23 毫秒
1.
2.
《Human immunology》2015,76(9):667-672
Both GLP17–36 (via GLP1 receptor) and the dipeptidyl peptidase-4 (DPP4) cleaved form of GLP1 (GLP19–36, independently of GLP1R) may modulate the response of lymphocytes to cytokine stimuli. The incretin axis, CXCR3 (receptor of DPP4 ligand cytokines CXCL9–11) expression on Tregs and hematologic parameters were assessed in 34 patients with long standing type 1 diabetes (T1DM) and in 35 healthy controls. Serum DPP4 (sDPP4) activity, plasma total GLP1 and GLP17–36 concentrations were determined. GLP19–36 concentrations were calculated. CXCR3 expression (flow cytometry) was higher on the CD25−/lowFoxp3+ than on the CD25+Foxp3+ Tregs independently from T1DM, suggesting that CD25−/lowFoxp3+ Tregs are possibly waiting for orientational chemotactic stimuli in a “standby mode”. The higher sDPP4 activities in T1DM were inversely correlated with GLP17–36 levels and GLP19–36 levels directly with lymphocyte counts in controls. Our results might indicate an altered DPP4-incretin system and altered immunoregulation including a potentially dysfunctional GLP19–36 signaling in T1DM. 相似文献
3.
4.
What is known and Objective: The prevalence of diabetes is increasing worldwide. Over the recent years, new discoveries have led to the development of new pharmacological agents targeting the incretin hormones gastric inhibitory peptide (GIP) and glucagon‐like peptide‐1 (GLP‐1). These agents, called incretin‐mimetics, are the newest agents added to the diabetes treatment options. The purpose of this article is to review the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions and place in therapy of liraglutide in the treatment of type 2 diabetes. Methods: An extensive search of the literature was performed with liraglutide and NN2211 as key terms. This article presents a review of the literature related to the chemistry, pharmacology, pharmacokinetics, drug interactions and safety and efficacy of liraglutide. Results and Discussion: Liraglutide, a subcutaneously administered GLP‐1 agonist, displays phamacodynamic and pharmacokinetic properties that allow for once‐daily administration. The agent has been shown to be efficacious as monotherapy, as well as in combination with glimperide, metformin and/or rosiglitazone, reducing glycoslyated haemoglobin (A1C) between 0·84% and 1·5%. The primary adverse event reported with liraglutide is transient nausea. What is new and conclusion: Liraglutide has been well studied in dual and triple combination therapies with sulfonylureas, metformin and rosiglitazone and appears safe and effective. For patients who cannot tolerate first‐line agents, metformin, insulin and sulfonylureas, liraglutide is a reasonable treatment option. 相似文献
5.
Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats 下载免费PDF全文
R. Saito M. So Y. Motojima T. Matsuura M. Yoshimura H. Hashimoto Y. Yamamoto K. Kusuhara Y. Ueta 《Journal of neuroendocrinology》2016,28(9)
Peripheral anorectic hormones, such as glucagon‐like peptide (GLP)‐1, cholecystokinin (CCK)‐8 and leptin, suppress food intake. The newly‐identified anorectic neuropeptide, nesfatin‐1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP‐1 and CCK‐8 and co‐administrations of GLP‐1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin‐1‐immunoreactive (‐IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP‐1 (100 μg/kg) caused significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK‐8 (50 μg/kg) resulted in marked increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP‐1 (33 μg/kg) or leptin. However, co‐administration of GLP‐1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP‐1, CCK‐8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin‐1. These results indicate that nesfatin‐1‐expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP‐1 and leptin in addition to CCK‐8, and also suppress food intake in rats. 相似文献
6.
The preweaning piglet has been found to be a valuable research model for testing ingredients used in infant formula. As part of the safety assessment, the neonates' immune system is an important component that has to be evaluated. In this study three concurrent strategies were developed to assess immune system status. The methods included (1) immunophenotying to assess circulating innate immune cell populations, (2) monitoring of circulating cytokines, particularly in response to a positive control agent, and (3) monitoring of localized gastrointestinal tissue cytokines using immunohistochemistry (IHC), particularly in response to a positive control agent. All assays were validated using white papers and regulatory guidance within a GLP environment. To validate the assays precision, accuracy and sample stability were evaluated as needed using a fit for purpose approach. In addition animals were treated with proinflammtory substances to detect a positive versus negative signal. In conclusion, these three methods were confirmed to be robust assays to evaluate the immune system and GIT-specific immune responses of preweaning piglets. 相似文献
7.
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of ∼850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses. 相似文献
8.
“Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA) was a comprehensive “industry-standard” Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically – and toxicologically – relevant. 相似文献
9.
Naohiro Ikeda Kenkichi FujiiMiko Sarada Hitoshi SaitoMasayoshi Kawabata Kiyoko NaruseKatsuyuki Yuki Hideaki NakagiriHiroshi Honda Yasushi TamakiNaohiro Nishiyama Toshio Kasamatsu 《Food and chemical toxicology》2012
Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen. 相似文献
10.