全文获取类型
收费全文 | 1920篇 |
免费 | 133篇 |
专业分类
2053篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 28篇 |
2020年 | 23篇 |
2019年 | 49篇 |
2018年 | 45篇 |
2017年 | 42篇 |
2016年 | 73篇 |
2015年 | 109篇 |
2014年 | 110篇 |
2013年 | 143篇 |
2012年 | 166篇 |
2011年 | 140篇 |
2010年 | 94篇 |
2009年 | 93篇 |
2008年 | 126篇 |
2007年 | 123篇 |
2006年 | 102篇 |
2005年 | 101篇 |
2004年 | 98篇 |
2003年 | 77篇 |
2002年 | 75篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 20篇 |
1997年 | 22篇 |
1996年 | 18篇 |
1995年 | 19篇 |
1994年 | 18篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
排序方式: 共有2053条查询结果,搜索用时 0 毫秒
991.
Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits 总被引:4,自引:0,他引:4
Scuteri A Sanna S Chen WM Uda M Albai G Strait J Najjar S Nagaraja R Orrú M Usala G Dei M Lai S Maschio A Busonero F Mulas A Ehret GB Fink AA Weder AB Cooper RS Galan P Chakravarti A Schlessinger D Cao A Lakatta E Abecasis GR 《PLoS genetics》2007,3(7):e115
The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 ×10−7), hip circumference (p = 3.4 × 10−8), and weight (p = 9.1 × 10−7). In Sardinia, homozygotes for the rare “G” allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common “A” allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 × 10−6). Homozygotes for the rare “A” allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common “G” allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare “A” allele were, on average, 1.0–3.0 BMI units heavier than homozygotes for the more common “G” allele. In summary, we have completed a whole genome–association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population. 相似文献
992.
Irene Matera Antonella Gullotto Silvia Tilli Marta Ferraroni Andrea Scozzafava Fabrizio Briganti 《Inorganica chimica acta》2008,361(14-15):4129-4137
A multicopper oxidase, the fungal laccase glycoenzyme from the white-rot basidiomycete fungus Trametes (Funalia) trogii, was crystallized and its crystal structure was solved at 1.58 Å using molecular replacement techniques.Model refinement resulted in R-factor and R-free values of 17.4% and 19.0%, respectively. The T. trogii laccase structural model reveals the presence of a ligand bound to the T1 active site which resembles a p-toluate molecule, such bound compound is most probably a fungal metabolite. The p-toluate is bound into the T1 active site of the laccase forming, with one of the carboxylate oxygens, a H-bond with His455, one of the T1 copper ion ligands, whereas the methyl group presents hydrophobic interactions within a pocket composed by Phe331, Phe336, Pro390 and Val162.The coordination geometries, the bond distances and the oxidation states of the T1 and T2/T3 copper active sites are analyzed and discussed in terms of the enzymatic mechanism and catalytic functionality. 相似文献
993.
994.
995.
Paola Spessotto Antonella Zucchetto Massimo Degan Bruna Wasserman Carla Danussi Riccardo Bomben Roberto Perris Vincenzo Canzonieri Oriano Radillo Alfonso Colombatti Valter Gattei 《Matrix biology》2007,26(6):473-484
Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments. 相似文献
996.
Antonella Preti Ken MacKenzie Kate A. Spivey Leslie R. Noble Catherine S. Jones Ralph G. Appy Graham J. Pierce 《Journal of fish biology》2020,97(2):354-361
This study documented the parasite faunas of the spiral valves of blue sharks Prionace glauca (L. 1758) and common thresher sharks Alopias vulpinus (Bonnaterre, 1788) caught in the California Current Large Marine Ecosystem (CCLME) north of the Mexican border. The spiral valves of 18 blue and 19 thresher sharks caught in the CCLME from 2009 to 2013 were examined for parasites. Seven parasite taxa were found in blue sharks and nine in threshers. The tetraphyllidean cestode Anthobothrium sp. (78% prevalence) was the most common parasite in blue sharks, and the phyllobothriid cestode Paraorygmatobothrium sp. (90% prevalence) was the most common in threshers. An adult nematode of the genus Piscicapillaria was found in threshers for the first time and may be a new species. Adult individuals of Hysterothylacium sp. were found in both shark species. The adult acanthocephalan Rhadinorhynchus cololabis and remains of the parasitic copepod Pennella sp. – both parasites of Pacific saury, Cololabis saira – were found in the intestines of threshers, indicating recent feeding on saury. This study paves the way for a more comprehensive examination, including more samples and a wider variety of shark species, to provide a greater understanding of shark feeding behaviour and possibly provide information on shark population biology. 相似文献
997.
Anna Manara Elisa Fasani Antonella Furini Giovanni DalCorso 《Plant, cell & environment》2020,43(12):2969-2986
To succeed in life, living organisms have to adapt to the environmental issues to which they are subjected. Some plants, defined as hyperaccumulators, have adapted to metalliferous environments, acquiring the ability to tolerate and accommodate high amounts of toxic metal into their shoot, without showing symptoms of toxicity. The determinants for these traits and their mode of action have long been the subject of research, whose attention lately moved to the evolution of the hypertolerance and hyperaccumulation traits. Genetic evidence indicates that the evolution of both traits includes significant evolutionary events that result in species-wide tolerant and accumulating backgrounds. Different edaphic environments are responsible for subsequent refinement, by local adaptive processes, leading to specific strategies and various degrees of hypertolerance and hyperaccumulation, which characterize metallicolous from non-metallicolous ecotypes belonging to the same genetic unit. In this review, we overview the most updated concepts regarding the evolution of hyperaccumulation and hypertolerance, highlighting also the ecological context concerning the plant populations displaying this fascinating phenomenon. 相似文献
998.
Luana Palazzi Antonella Pasquato Mattia Vicario Alexandre Roulin Patrizia Polverino de Laureto Laura Cendron 《Journal of peptide science》2020,26(11)
Peptides are attractive drugs because of their specificity and minimal off‐target effects. Short half‐lives are within their major drawbacks, limiting actual use in clinics. The golden standard in therapeutic peptide development implies identification of a minimal core sequence, then modified to increase stability through several strategies, including the introduction of nonnatural amino acids, cyclization, and lipidation. Here, we investigated plasma degradations of hormone sequences all composed of a minimal active core peptide and a C‐terminal extension. We first investigated pro‐opimelanocortin (POMC) γ2/γ3‐MSH hormone behavior and extended our analysis to POMC‐derived α‐melanocyte stimulating hormone/adrenocorticotropic hormone signaling neuropeptides and neurotensin. We demonstrated that in all the three cases analyzed in this study, few additional residues mimicking the natural sequence alter both peptide stability and the mechanism(s) of degradation of the minimal conserved functional pattern. Our results suggest that the impact of extensions on the bioactivity of a peptide drug has to be carefully evaluated throughout the optimization process. 相似文献
999.
Marianna Avitabile Vito Alessandro Lasorsa Sueva Cantalupo Antonella Cardinale Flora Cimmino Annalaura Montella Dalila Capasso Riccardo Haupt Loredana Amoroso Alberto Garaventa Alessandro Quattrone Maria Valeria Corrias Achille Iolascon Mario Capasso 《Journal of cellular and molecular medicine》2020,24(7):4072-4081