全文获取类型
收费全文 | 429篇 |
免费 | 50篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 18篇 |
2021年 | 33篇 |
2020年 | 22篇 |
2019年 | 10篇 |
2018年 | 22篇 |
2017年 | 14篇 |
2016年 | 33篇 |
2015年 | 35篇 |
2014年 | 39篇 |
2013年 | 38篇 |
2012年 | 37篇 |
2011年 | 35篇 |
2010年 | 25篇 |
2009年 | 24篇 |
2008年 | 26篇 |
2007年 | 17篇 |
2006年 | 8篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1979年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 46 毫秒
101.
102.
Sabyasachi Das Masayuki Hirano Rea Tako Chelsea McCallister Nikolas Nikolaidis 《Current Genomics》2012,13(2):95-102
Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. 相似文献
103.
104.
Nicholas Ho Hui Peng Chelsea Mayoh Pei Y. Liu Bernard Atmadibrata Glenn M. Marshall 《Cell cycle (Georgetown, Tex.)》2018,17(6):749-758
Neuroblastoma, the most common solid tumour in early childhood, is characterized by very frequent chromosomal copy number variations (CNVs). While chromosome 2p amplification, 17q gain, 1p and 11q deletion in human neuroblastoma tissues are well-known, the exact frequencies and boundaries of the chromosomal CNVs have not been delineated. We analysed the publicly available single nucleotide polymorphism (SNP) array data which were originally generated by the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative, defined the frequencies and boundaries of chromosomes 2p11.2 – 2p25.3 amplification, 17q11.1-17q25.3 gain, 1p13.3-1p36.33 deletion and 11q13.3-11q25 deletion in neuroblastoma tissues, and identified chromosome 7q14.1 (Chr7:38254795-38346971) and chromosome 14q11.2 (Chr14:21637401-22024617) deletion in blood and bone marrow samples from neuroblastoma patients, but not in tumour tissues. Kaplan Meier analysis showed that double deletion of Chr7q14.1 and Chr14q11.2 correlated with poor prognosis in MYCN gene amplified neuroblastoma patients. In conclusion, the oncogenes amplified or gained and tumour suppressor genes deleted within the boundaries of chromosomal CNVs in tumour tissues should be studied for their roles in tumourigenesis and as therapeutic targets. Focal deletions of Chr7q14.1 and Chr14q11.2 together in blood and bone marrow samples from neuroblastoma patients can be used as a marker for poorer prognosis and more aggressive therapies. 相似文献
105.
Jamie L. Rothenburger Chelsea G. Himsworth Nicole M. Nemeth David L. Pearl Claire M. Jardine 《EcoHealth》2018,15(1):82-95
Worldwide, Norway rats (Rattus norvegicus) carry a number of zoonotic pathogens. Many studies have identified rat-level risk factors for pathogen carriage. The objective of this study was to examine associations between abundance, microenvironmental and weather features and Clostridium difficile, antimicrobial-resistant (AMR) Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) carriage in urban rats. We assessed city blocks for rat abundance and 48 microenvironmental variables during a trap-removal study, then constructed 32 time-lagged temperature and precipitation variables and fitted multivariable logistic regression models. The odds of C. difficile positivity were significantly lower when mean maximum temperatures were high (≥ 12.89°C) approximately 3 months before rat capture. Alley pavement condition was significantly associated with AMR E. coli. Rats captured when precipitation was low (< 49.40 mm) in the 15 days before capture and those from blocks that contained food gardens and institutions had increased odds of testing positive for MRSA. Different factors were associated with each pathogen, which may reflect varying pathogen ecology including exposure and environmental survival. This study adds to the understanding of how the microenvironment and weather impacts the epidemiology and ecology of zoonotic pathogens in urban ecosystems, which may be useful for surveillance and control activities. 相似文献
106.
Petra Lassuthova Adriana P. Rebelo Gianina Ravenscroft Phillipa J. Lamont Mark R. Davis Fiore Manganelli Shawna M. Feely Chelsea Bacon Dana Šafka Brožková Jana Haberlova Radim Mazanec Feifei Tao Cima Saghira Lisa Abreu Steve Courel Eric Powell Elena Buglo Dana M. Bis Stephan Zuchner 《American journal of human genetics》2018,102(3):505-514
107.
108.
109.
110.
Seventy-kilodalton heat shock proteins (Hsp70s) are molecular chaperones essential for maintaining cellular homeostasis. Apart from their indispensable roles in protein homeostasis, specific Hsp70s localize at the plasma membrane and bind to specific lipids. The interaction of Hsp70s with lipids has direct physiological outcomes including lysosomal rescue, microautophagy, and promotion of cell apoptosis. Despite these essential functions, the Hsp70-lipid interactions remain largely uncharacterized. In this study, we characterized the interaction of HspA1A, an inducible Hsp70, with five phospholipids. We first used high concentrations of potassium and established that HspA1A embeds in membranes when bound to all anionic lipids tested. Furthermore, we found that protein insertion is enhanced by increasing the saturation level of the lipids. Next, we determined that the nucleotide-binding domain (NBD) of the protein binds to lipids quantitatively more than the substrate-binding domain (SBD). However, for all lipids tested, the full-length protein is necessary for embedding. We also used calcium and reaction buffers equilibrated at different pH values and determined that electrostatic interactions alone may not fully explain the association of HspA1A with lipids. We then determined that lipid binding is inhibited by nucleotide-binding, but it is unaffected by protein-substrate binding. These results suggest that the HspA1A lipid-association is specific, depends on the physicochemical properties of the lipid, and is mediated by multiple molecular forces. These mechanistic details of the Hsp70-lipid interactions establish a framework of possible physiological functions as they relate to chaperone regulation and localization.