全文获取类型
收费全文 | 463篇 |
免费 | 33篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 20篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 10篇 |
2017年 | 14篇 |
2016年 | 20篇 |
2015年 | 18篇 |
2014年 | 18篇 |
2013年 | 25篇 |
2012年 | 35篇 |
2011年 | 41篇 |
2010年 | 11篇 |
2009年 | 15篇 |
2008年 | 22篇 |
2007年 | 31篇 |
2006年 | 20篇 |
2005年 | 29篇 |
2004年 | 15篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 9篇 |
2000年 | 11篇 |
1999年 | 10篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 9篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有496条查询结果,搜索用时 203 毫秒
61.
GA Bezerra E Dobrovetsky A Dong A Seitova L Crombett LM Shewchuk AM Hassell SM Sweitzer TD Sweitzer PJ McDevitt KO Johanson KM Kennedy-Wilson D Cossar A Bochkarev K Gruber S Dhe-Paganon 《PloS one》2012,7(8):e43019
Proline-specific dipeptidyl peptidases (DPPs) are emerging targets for drug development. DPP4 inhibitors are approved in many countries, and other dipeptidyl peptidases are often referred to as DPP4 activity- and/or structure-homologues (DASH). Members of the DASH family have overlapping substrate specificities, and, even though they share low sequence identity, therapeutic or clinical cross-reactivity is a concern. Here, we report the structure of human DPP7 and its complex with a selective inhibitor Dab-Pip (L-2,4-diaminobutyryl-piperidinamide) and compare it with that of DPP4. Both enzymes share a common catalytic domain (α/β-hydrolase). The catalytic pocket is located in the interior of DPP7, deep inside the cleft between the two domains. Substrates might access the active site via a narrow tunnel. The DPP7 catalytic triad is completely conserved and comprises Ser162, Asp418 and His443 (corresponding to Ser630, Asp708 and His740 in DPP4), while other residues lining the catalytic pockets differ considerably. The "specificity domains" are structurally also completely different exhibiting a β-propeller fold in DPP4 compared to a rare, completely helical fold in DPP7. Comparing the structures of DPP7 and DPP4 allows the design of specific inhibitors and thus the development of less cross-reactive drugs. Furthermore, the reported DPP7 structures shed some light onto the evolutionary relationship of prolyl-specific peptidases through the analysis of the architectural organization of their domains. 相似文献
62.
JL Proenca-Modena FC Pereira Valera MG Jacob GP Buzatto TH Saturno L Lopes JM Souza FE Paula ML Silva LR Carenzi E Tamashiro E Arruda WT Anselmo-Lima 《PloS one》2012,7(8):e42136
Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases. 相似文献
63.
The isoprenoid metabolic pathway in protozoa of the Leishmania genus exhibits distinctive characteristics. These parasites, as well as other members of the Trypanosomatidae family, synthesize ergosterol, instead of cholesterol, as the main membrane sterol lipid. Leishmania has been shown to utilize leucine, instead of acetate as the main precursor for sterol biosynthesis. While mammalian dolichols are molecules containing 15-23 isoprene units, Leishmania amazonensis promastigotes synthesize dolichol of 11 and 12 units. In this paper, we show that the intracellular stages of L. amazonensis, amastigotes, synthesize mainly polyprenols of 9 isoprene units, instead of dolichol. 相似文献
64.
In an effort to reduce feed costs, many pork producers have increased their use of coproducts of biofuel production in commercial pig diets, including increased feeding of distiller’s dried grains with solubles (DDGS). The inclusion of DDGS increases the insoluble fiber content in the ration, which has the potential to impact the colonic microbiota considerably as the large intestine contains a dynamic microenvironment with tremendous interplay between microorganisms. Any alteration to the physical or chemical properties of the colonic contents has the potential to impact the resident bacterial population and potentially favor or inhibit the establishment of pathogenic species. In the present study, colonic contents collected at necropsy from pigs fed either 30% or no DDGS were analyzed to examine the relative abundance of bacterial taxa associated with feeding this ingredient. No difference in alpha diversity (richness) was detected between diet groups. However, the beta diversity was significantly different between groups with feeding of DDGS being associated with a decreased Firmicutes:Bacteriodetes ratio (P = .004) and a significantly lower abundance of Lactobacillus spp. (P = .016). Predictive functional profiling of the microbiota revealed more predicted genes associated with carbohydrate metabolism, protein digestion, and degradation of glycans in the microbiota of pigs fed DDGS. Taken together, these findings confirm that alterations in dietary insoluble fiber significantly alter the colonic microbial profile of pigs and suggest the resultant microbiome may predispose to the development of colitis. 相似文献
65.
66.
67.
68.
69.
70.