全文获取类型
收费全文 | 213篇 |
免费 | 13篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 1篇 |
妇产科学 | 10篇 |
基础医学 | 71篇 |
口腔科学 | 9篇 |
临床医学 | 16篇 |
内科学 | 29篇 |
皮肤病学 | 3篇 |
神经病学 | 4篇 |
特种医学 | 6篇 |
外科学 | 14篇 |
一般理论 | 1篇 |
预防医学 | 9篇 |
眼科学 | 4篇 |
药学 | 30篇 |
中国医学 | 1篇 |
肿瘤学 | 18篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 4篇 |
2012年 | 15篇 |
2011年 | 23篇 |
2010年 | 11篇 |
2009年 | 9篇 |
2008年 | 22篇 |
2007年 | 22篇 |
2006年 | 10篇 |
2005年 | 17篇 |
2004年 | 17篇 |
2003年 | 18篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
排序方式: 共有227条查询结果,搜索用时 15 毫秒
1.
2.
Stolnik Snjezana Dunn Susan E. Garnett Martin C. Davies Martyn C. Coombes Allan G. A. Taylor D. C. Irving M. P. Purkiss S. C. Tadros T. F. Davis Stanley S. Illum Lisbeth 《Pharmaceutical research》1994,11(12):1800-1808
The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour. 相似文献
3.
Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy 总被引:1,自引:0,他引:1
4.
Consistent copy number changes and recurrent PRKAR1A mutations distinguish Melanotic Schwannomas from Melanomas: SNP‐array and next generation sequencing analysis 下载免费PDF全文
Lu Wang Ahmet Zehir Justyna Sadowska Nengyi Zhou Marc Rosenblum Klaus Busam Narasimhan Agaram William Travis Maria Arcila Snjezana Dogan Michael F. Berger Donavan T. Cheng Marc Ladanyi Khedoudja Nafa Meera Hameed 《Genes, chromosomes & cancer》2015,54(8):463-471
Melanotic Schwannomas (MS) are rare tumors that share histological features with melanocytic tumors and schwannomas. However, their genetics are poorly understood. To elucidate the genetic characteristics of MS, we performed genome‐wide studies in a series of cases. Twelve MS cases were available for the study. Genomic DNAs extracted from formalin‐fixed paraffin embedded tumor tissues were subjected to copy number (CN) and allelic imbalance (AI) analysis by Single Nucleotide Polymorphism (SNP)‐array and screened for mutations in coding exons of 341 key cancer‐associated genes using a hybrid capture‐based next‐generation sequencing (NGS) assay. Sanger sequencing was used to further verify recurrent mutations detected by NGS study. SNP‐array analysis revealed remarkably stereotypic chromosomal abnormalities in MS. Hypodiploidy was common, typically involving monosomies of chromosomes 1, 2, and 17. All 12 samples showed mutations in PRKAR1A gene, including 2 cases with 2 mutations each. The 14 mutations were scattered across PRKAR1A, and most were inactivating mutations. AI on 17q, presenting as loss of heterozygosity with or without CN losses, combined with a PRKAR1A mutation was observed in 9/12 MS cases. The remaining 3 cases included the two samples harboring two mutations in PRKAR1A. MS exhibits a stereotypic pattern of chromosomal losses. In contrast, melanomas are typically characterized by the presence of multiple CN aberrations, without demonstrable differences in the frequency of losses and gains. Inactivation of both alleles of PRKAR1A by “two hits” observed in almost all cases underscores the central role of PRKAR1A in the pathogenesis of this neoplasm. © 2015 Wiley Periodicals, Inc. 相似文献
5.
Rothkrantz-Kos S Drent M Rutgers A Heeringa P De Vries J van Dieijen-Visser MP Cohen Tervaert JW 《European Journal of Internal Medicine》2003,14(5):296-301
Previously, we demonstrated that the number of polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid (BALF) is useful in distinguishing sarcoidosis patients with a favorable outcome from those having a more severe course of disease. Neutrophils contain the oxidant-generating enzyme myeloperoxidase (MPO). Cellular levels of MPO can be influenced by functional promotor polymorphisms, ?463G/A and ?129G/A, which may modify disease severity. 相似文献
6.
Hechtman Jaclyn Frances DeMatteo Ronald Nafa Khedoudja Chi Ping Arcila Maria E. Dogan Snjezana Oultache Alifya Chen Wen Hameed Meera 《Annals of surgical oncology》2015,22(8):2633-2639
Annals of Surgical Oncology - The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic... 相似文献
7.
8.
9.
Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes
Gilbert MT Drautz DI Lesk AM Ho SY Qi J Ratan A Hsu CH Sher A Dalén L Götherström A Tomsho LP Rendulic S Packard M Campos PF Kuznetsova TV Shidlovskiy F Tikhonov A Willerslev E Iacumin P Buigues B Ericson PG Germonpré M Kosintsev P Nikolaev V Nowak-Kemp M Knight JR Irzyk GP Perbost CS Fredrikson KM Harkins TT Sheridan S Miller W Schuster SC 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(24):8327-8332
We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximately 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the (14)C ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep. 相似文献
10.