全文获取类型
收费全文 | 622篇 |
免费 | 34篇 |
出版年
2023年 | 4篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 21篇 |
2013年 | 29篇 |
2012年 | 33篇 |
2011年 | 46篇 |
2010年 | 29篇 |
2009年 | 25篇 |
2008年 | 31篇 |
2007年 | 32篇 |
2006年 | 40篇 |
2005年 | 34篇 |
2004年 | 40篇 |
2003年 | 26篇 |
2002年 | 17篇 |
2001年 | 19篇 |
2000年 | 19篇 |
1999年 | 15篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1970年 | 6篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1966年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有656条查询结果,搜索用时 15 毫秒
101.
Hye Mi Kim Boonjae Jang Young Eun Cheon Myunghyun Paik Suh Junghun Suh 《Journal of biological inorganic chemistry》2009,14(1):151-157
Catalytic drugs based on target-selective artificial proteases have been proposed as a new paradigm in drug design. Peptide-cleavage
agents selective for pathogenic proteins of Alzheimer’s disease, type 2 diabetes mellitus or Parkinson’s disease have been
prepared using the Co(III) aqua complex (Co(III)cyclen) of 1,4,7,10-tetraazacyclododecane as the catalytic center. In the
present study, the Co(III) aqua complex (Co(III)oxacyclen) of 1-oxa-4,7,10-triazacyclododecane was examined in search of an
improved catalytic center for peptide-cleavage agents. An X-ray crystallographic study of [Co(oxacyclen)(CO3)](ClO4), titration of Co(III)oxacyclen, and kinetic studies on the cleavage of albumin, γ-globulin, lysozyme, and myoglobin by Co(III)oxacyclen
were carried out. Considerably higher proteolytic activity was observed for Co(III)oxacyclen in comparison with Co(III)cyclen,
indicating that better target-selective artificial metalloproteases would be obtained using Co(III)oxacyclen as the catalytic
center. The improved proteolytic activity was attributed to either steric effects or the increased Lewis acidity of the Co(III)
center. The kinetic data also predicted that side effects due to the cleavage of nontarget proteins by a catalytic drug based
on Co(III)oxacyclen would be insignificant. 相似文献
102.
Hyoung‐Joo Lee Keun Na Min‐Seok Kwon Hoguen Kim Kyoung Sik Kim Young‐Ki Paik 《Proteomics》2009,9(12):3395-3408
Reversible phosphorylation of proteins is the most common PTM in cell‐signaling pathways. Despite this, high‐throughput methods for the systematic detection, identification, and quantification of phosphorylated peptides have yet to be developed. In this paper, we describe the establishment of an efficient online titaniuim dioxide (TiO2)‐based 3‐D LC (strong cationic exchange/TiO2/C18)‐MS3‐linear ion trap system, which provides fully automatic and highly efficient identification of phosphorylation sites in complex peptide mixtures. Using this system, low‐abundance phosphopeptides were isolated from cell lines, plasma, and tissue of healthy and hepatocellular carcinoma (HCC) patients. Furthermore, the phosphorylation sites were identified and the differences in phosphorylation levels between healthy and HCC patient specimens were quantified by labeling the phosphopeptides with isotopic analogs of amino acids (stable isotope labeling with amino acids in cell culture for HepG2 cells) or water (HO for tissues and plasma). Two examples of potential HCC phospho‐biomarkers including plectin‐1(phopho‐Ser‐4253) and alpha‐HS‐glycoprotein (phospho‐Ser 138 and 312) were identified by this analysis. Our results suggest that this comprehensive TiO2‐based online‐3‐D LC‐MS3‐linear ion trap system with high‐throughput potential will be useful for the global profiling and quantification of the phosphoproteome and the identification of disease biomarkers. 相似文献
103.
104.
105.
Kim EJ Sung JY Lee HJ Rhim H Hasegawa M Iwatsubo T Min do S Kim J Paik SR Chung KC 《The Journal of biological chemistry》2006,281(44):33250-33257
Lewy bodies (LBs) are pathological hallmarks of Parkinson disease (PD) but also occur in Alzheimer disease (AD) and dementia of LBs. Alpha-synuclein, the major component of LBs, is observed in the brain of Down syndrome (DS) patients with AD. Dyrk1A, a dual specificity tyrosine-regulated kinase (Dyrk) family member, is the mammalian ortholog of the Drosophila minibrain (Mnb) gene, essential for normal postembryonic neurogenesis. The Dyrk1A gene resides in the human chromosome 21q22.2 region, which is associated with DS anomalies, including mental retardation. In this study, we examined whether Dyrk1A interacts with alpha-synuclein and subsequently affects intracellular alpha-synuclein inclusion formation in immortalized hippocampal neuronal (H19-7) cells. Dyrk1A selectively binds to alpha-synuclein in transformed and primary neuronal cells. Alpha-synuclein overexpression, followed by basic fibroblast growth factor-induced neuronal differentiation, resulted in cell death. We observed that accompanying cell death was increased alpha-synuclein phosphorylation and intracytoplasmic aggregation. In addition, the transfection of kinase-inactive Dyrk1A or Dyrk1A small interfering RNA blocked alpha-synuclein phosphorylation and aggregate formation. In vitro kinase assay of anti-Dyrk1A immunocomplexes demonstrated that Dyrk1A could phosphorylate alpha-synuclein at Ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by Dyrk1A, potentially affecting neuronal cell viability. 相似文献
106.
107.
Minkoo Ahn Sungsoo Kang Hee Jung Koo Jung‐Ho Lee Yoon‐Sik Lee Seung R. Paik 《Biotechnology progress》2010,26(6):1759-1764
Amyloid fibrils are considered as novel nanomaterials because of their nanoscale width, a regular constituting structure of cross β‐sheet conformation, and considerable mechanical strength. By using an amyloidogenic protein of β2‐microglobulin (β2M) related to dialysis‐related amyloidosis, nanoporous protein matrix has been prepared. The β2M granules made of around 15 monomers showed an average size of 23.1 nm. They formed worm‐like fibrils at pH 7.4 in 20 mM sodium phosphate containing 0.15 M NaCl following vigorous nondirectional shaking incubation, in which they became laterally associated and interwound to generate the porous amyloid fibrillar matrix with an average pore size of 30–50 nm. This nanoporous protein matrix was demonstrated to be selectively disintegrated by reducing agents, such as tris‐(2‐carboxyethyl) phosphine. High surface area with nanopores on the surface has been suggested to make the matrix of β2M amyloid fibrils particularly suitable for applications in the area of nanobiotechnology including drug delivery and tissue engineering. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献
108.
109.
110.
Cho YJ Choi JK Kim JH Lim YS Ham JS Kang DK Chun J Paik HD Kim GB 《Journal of bacteriology》2011,193(18):5021-5022
The draft genome sequence of Lactobacillus salivarius GJ-24 isolated from the feces of healthy adults was determined. Its properties, including milk fermentation activity and bacteriocin production, suggest its potential uses as a probiotic lactic acid bacterium and start culture for dairy products. 相似文献