全文获取类型
收费全文 | 168篇 |
免费 | 9篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 14篇 |
2014年 | 11篇 |
2013年 | 13篇 |
2012年 | 15篇 |
2011年 | 15篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 10篇 |
2007年 | 9篇 |
2006年 | 8篇 |
2005年 | 13篇 |
2004年 | 13篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 1篇 |
1999年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有177条查询结果,搜索用时 31 毫秒
21.
Forns P Esteve C Taboada L Alonso JA Orellana A Maldonado M Carreño C Ramis I López M Miralpeix M Vidal B 《Bioorganic & medicinal chemistry letters》2012,22(8):2784-2788
A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay. 相似文献
22.
Do TQ Moshkani S Castillo P Anunta S Pogosyan A Cheung A Marbois B Faull KF Ernst W Chiang SM Fujii G Clarke CF Foster K Porter E 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(6):4177-4187
Mucosal surfaces provide first-line defense against microbial invasion through their complex secretions. The antimicrobial activities of proteins in these secretions have been well delineated, but the contributions of lipids to mucosal defense have not been defined. We found that normal human nasal fluid contains all major lipid classes (in micrograms per milliliter), as well as lipoproteins and apolipoprotein A-I. The predominant less polar lipids were myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acid, cholesterol, and cholesteryl palmitate, cholesteryl linoleate, and cholesteryl arachidonate. Normal human bronchioepithelial cell secretions exhibited a similar lipid composition. Removal of less-polar lipids significantly decreased the inherent antibacterial activity of nasal fluid against Pseudomonas aeruginosa, which was in part restored after replenishing the lipids. Furthermore, lipids extracted from nasal fluid exerted direct antibacterial activity in synergism with the antimicrobial human neutrophil peptide HNP-2 and liposomal formulations of cholesteryl linoleate and cholesteryl arachidonate were active against P. aeruginosa at physiological concentrations as found in nasal fluid and exerted inhibitory activity against other Gram-negative and Gram-positive bacteria. These data suggest that host-derived lipids contribute to mucosal defense. The emerging concept of host-derived antimicrobial lipids unveils novel roads to a better understanding of the immunology of infectious diseases. 相似文献
23.
Marieta V Pancheva Vladimir S Panchev Adelina V Suvandjieva 《Journal of applied physiology》2006,100(3):1090; author reply 1091-1090; author reply 1092
24.
25.
To explain the etiology and find a mode of therapy of genetically determined low levels of high-density lipoprotein (HDL), we have generated recombinant adenoviruses expressing apolipoprotein A-I (apoA-I)(Leu141Arg)Pisa and apoA-I(Leu159Arg)FIN and studied their properties in vitro and in vivo. Both mutants were secreted efficiently from cells but had diminished capacity to activate lecithin/cholesterol acyltransferase (LCAT) in vitro. Adenovirus-mediated gene transfer of either of the two mutants in apoA-I-deficient (apoA-I-/-) mice resulted in greatly decreased total plasma cholesterol, apoA-I, and HDL cholesterol levels. The treatment also decreased the cholesteryl ester to total cholesterol ratio (CE/TC), caused accumulation of prebeta1-HDL and small size alpha4-HDL particles, and generated only few spherical HDL particles, as compared to mice expressing wild-type (WT) apoA-I. Simultaneous treatment of the mice with adenoviruses expressing either of the two mutants and human LCAT normalized the plasma apoA-I, HDL cholesterol levels, and the CE/TC ratio, restored normal prebeta- and alpha-HDL subpopulations, and generated spherical HDL. The study establishes that apoA-I(Leu141Arg)Pisa and apoA-I(Leu159Arg)FIN inhibit an early step in the biogenesis of HDL due to inefficient esterification of the cholesterol of the prebeta1-HDL particles by the endogenous LCAT. Both defects can be corrected by treatment with LCAT. 相似文献
26.
Nancy A. Rodriguez Wei Si Adelina M. Emmi Lawrence C. Layman Ali Eroglu 《Molecular reproduction and development》2009,76(9):890-896
Oocytes of nonhuman primates such as rhesus monkeys are excellent models for diverse studies on developmental biology, epigenetics, human reproduction, and assisted reproductive technologies, as well as on transgenics. Such studies require numerous oocytes that can be retrieved after controlled ovarian stimulation. Currently, most primate centers use laparoscopic aspiration or laparotomy followed by aspiration to collect rhesus oocytes, although the ultrasound‐guided needle aspiration is more advantageous due to reduced infection risk, less injury, and a shorter recovery period. Yet, some initial difficulties associated with the ultrasound‐guided needle aspiration limit its broader application. The objective of the present study was to address these obstacles. By presenting practical solutions to the initial difficulties, results from our study show that it is possible to collect a mean number of 38 ± 10 rhesus oocytes per hormonally stimulated female. These results compare favorably to the average number of rhesus oocytes collected using the laparoscopic approach and suggest that when initial obstacles are overcome, the ultrasound‐guided oocyte retrieval represents a good alternative to more invasive approaches. Mol. Reprod. Dev. 76: 890–896, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
27.
Adelina Maria Kühl Carmen Lúcia Mello Sartori Cardoso da Rocha Evaldo Luiz Gaeta Espíndola Fbio Amodêo Lansac‐Tha 《International Review of Hydrobiology》2010,95(3):260-272
The Pirapó river watershed (Paraná State, Brazil) compounds a relatively industrialized and urbanized region, undergoing great pressure from the discharge of industrial, agricultural and domestic wastes. We evaluated the environmental quality of ten streams belonging to this watershed in April and June 2008 by performing acute and chronic toxicity tests with Daphnia similis and Ceriodaphnia silvestrii from water and sediment samples. We tested the hypothesis that the streams located in urban areas are more exposed to the influence of pollutants, than those outside the city limits. In addition, we obtained the measures of physical and chemical parameters, and identified the main polluted sources. Contrary to what was expected, the rural streams were more toxic than those located in urban area. These results demonstrate that the water bodies located in rural areas are being affected by the pollution of aquatic ecosystems as far as those found in urban areas, requiring the same attention of environmental managers in relation to its monitoring. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
28.
29.
Kateifides AK Gorshkova IN Duka A Chroni A Kardassis D Zannis VI 《Journal of lipid research》2011,52(7):1363-1372
In this study, we investigated the role of positively and negatively charged amino acids within the 89-99 region of apolipoprotein A-I (apoA-I), which are highly conserved in mammals, on plasma lipid homeostasis and the biogenesis of HDL. We previously showed that deletion of the 89-99 region of apoA-I increased plasma cholesterol and phospholipids, but it did not affect plasma triglycerides. Functional studies using adenovirus-mediated gene transfer of two apoA-I mutants in apoA-I-deficient mice showed that apoA-I[D89A/E91A/E92A] increased plasma cholesterol and caused severe hypertriglyceridemia. HDL levels were reduced, and approximately 40% of the apoA-I was distributed in VLDL/IDL. The HDL consisted of mostly spherical and a few discoidal particles and contained preβ1 and α4-HDL subpopulations. The lipid, lipoprotein, and HDL profiles generated by the apoA-I[K94A/K96A] mutant were similar to those of wild-type (WT) apoA-I. Coexpression of apoA-I[D89A/E91A/E92A] and human lipoprotein lipase abolished hypertriglyceridemia, restored in part the α1,2,3,4 HDL subpopulations, and redistributed apoA-I in the HDL2/HDL3 regions, but it did not prevent the formation of discoidal HDL particles. Physicochemical studies showed that the apoA-I[D89A/E91A/E92A] mutant had reduced α-helical content and effective enthalpy of thermal denaturation, increased exposure of hydrophobic surfaces, and increased affinity for triglyceride-rich emulsions. We conclude that residues D89, E91, and E92 of apoA-I are important for plasma cholesterol and triglyceride homeostasis as well as for the maturation of HDL. 相似文献
30.