全文获取类型
收费全文 | 120篇 |
免费 | 5篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 7篇 |
2013年 | 9篇 |
2012年 | 9篇 |
2011年 | 5篇 |
2010年 | 7篇 |
2009年 | 5篇 |
2008年 | 9篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有125条查询结果,搜索用时 281 毫秒
101.
Background
Leucine-rich repeats are one of the more common modules found in proteins. The leucine-rich repeat consensus motif is LxxLxLxxNxLxxLxxLxxLxx- where the first 11–12 residues are highly conserved and the remainder of the repeat can vary in size Leucine-rich repeat proteins have been subdivided into seven subfamilies, none of which include members of the epidermal growth factor receptor or insulin receptor families despite the similarity between the 3D structure of the L domains of the type I insulin-like growth factor receptor and some leucine-rich repeat proteins. 相似文献102.
David M Markusic Niek P van Til Johan K Hiralall PJ Oude Ronald Elferink Jurgen Seppen 《BMC biotechnology》2009,9(1):85
Background
Lentiviral vectors are well suited for gene therapy because they can mediate long-term expression in both dividing and nondividing cells. However, lentiviral vectors seem less suitable for liver gene therapy because systemically administered lentiviral vectors are preferentially sequestered by liver macrophages. This results in a reduction of available virus and might also increase the immune response to the vector and vector products. 相似文献103.
Guang Song Emily M.Lee Jianbo Pan Miao Xu Hee-Sool Rho Yichen Cheng Nadia Whitt Shu Yang Jennifer Kouznetsova Carleen Klumpp-Thomas Samuel G.Michael Cedric Moore Ki-Jun Yoon Kimberly M.Christian Anton Simeonov Wenwei Huang Menghang Xia Ruili Huang Madhu Lal-Nag Hengli Tang Wei Zheng Jiang Qian Hongjun Song Guo-li Ming Heng Zhu 《基因组蛋白质组与生物信息学报(英文版)》2021,19(1):108-122
The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets. 相似文献
104.
Bayesian analysis of factorial experiments by mixture modelling 总被引:3,自引:0,他引:3
105.
Plamen L. Simeonov Jaime Gomez-Ramirez Pridi Siregar 《Progress in biophysics and molecular biology》2013
This paper summarizes the results in Integral Biomathics obtained to this moment and provides an outlook for future research in the field. 相似文献
106.
107.
Natalia J. Martinez Ganesha Rai Adam Yasgar Wendy A. Lea Hongmao Sun Yuhong Wang Diane K. Luci Shyh-Ming Yang Kana Nishihara Shunichi Takeda Mohiuddin Sagor Irina Earnshaw Tetsuya Okada Kazutoshi Mori Kelli Wilson Gregory J. Riggins Menghang Xia Maurizio Grimaldi Ajit Jadhav David J. Maloney Anton Simeonov 《PloS one》2016,11(8)
The endoplasmic reticulum (ER) is involved in Ca2+ signaling and protein folding. ER Ca2+ depletion and accumulation of unfolded proteins activate the molecular chaperone GRP78 (glucose-regulated protein 78) which in turn triggers the ER stress response (ERSR) pathway aimed to restore ER homeostasis. Failure to adapt to stress, however, results in apoptosis. We and others have shown that malignant cells are more susceptible to ERSR-induced apoptosis than their normal counterparts, implicating the ERSR as a potential target for cancer therapeutics. Predicated on these findings, we developed an assay that uses a GRP78 biosensor to identify small molecule activators of ERSR in glioma cells. We performed a quantitative high-throughput screen (qHTS) against a collection of ~425,000 compounds and a comprehensive panel of orthogonal secondary assays was formulated for stringent compound validation. We identified novel activators of ERSR, including a compound with a 2,9-diazaspiro[5.5]undecane core, which depletes intracellular Ca2+ stores and induces apoptosis-mediated cell death in several cancer cell lines, including patient-derived and 3D cultures of glioma cells. This study demonstrates that our screening platform enables the identification and profiling of ERSR inducers with cytotoxic activity and advocates for characterization of these compound in in vivo models. 相似文献
108.
Anton Simeonov Avanti Kulkarni Dorjbal Dorjsuren Ajit Jadhav Min Shen Daniel R. McNeill Christopher P. Austin David M. Wilson III 《PloS one》2009,4(6)
APE1 is the major nuclease for excising abasic (AP) sites and particular 3′-obstructive termini from DNA, and is an integral participant in the base excision repair (BER) pathway. BER capacity plays a prominent role in dictating responsiveness to agents that generate oxidative or alkylation DNA damage, as well as certain chain-terminating nucleoside analogs and 5-fluorouracil. We describe within the development of a robust, 1536-well automated screening assay that employs a deoxyoligonucleotide substrate operating in the red-shifted fluorescence spectral region to identify APE1 endonuclease inhibitors. This AP site incision assay was used in a titration-based high-throughput screen of the Library of Pharmacologically Active Compounds (LOPAC1280), a collection of well-characterized, drug-like molecules representing all major target classes. Prioritized hits were authenticated and characterized via two high-throughput screening assays – a Thiazole Orange fluorophore-DNA displacement test and an E. coli endonuclease IV counterscreen – and a conventional, gel-based radiotracer incision assay. The top, validated compounds, i.e. 6-hydroxy-DL-DOPA, Reactive Blue 2 and myricetin, were shown to inhibit AP site cleavage activity of whole cell protein extracts from HEK 293T and HeLa cell lines, and to enhance the cytotoxic and genotoxic potency of the alkylating agent methylmethane sulfonate. The studies herein report on the identification of novel, small molecule APE1-targeted bioactive inhibitor probes, which represent initial chemotypes towards the development of potential pharmaceuticals. 相似文献
109.
110.
Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations 总被引:22,自引:0,他引:22
Two precursor cell subpopulations have been isolated from the spleen cells of nonimmune mice. The major B cell subpopulation binds high levels of the J11D monoclonal antibody and, upon T cell-dependent antigenic stimulation, gives rise to primary antibody-forming cell clones but not secondary B cells. A minority of the 10%-14% of Ia+ precursors that bind low levels of J11D (J11Dlo) also generate antibody-forming cell clones after primary stimulation. However, over 70% of J11Dlo precursors yield no primary antibody-forming cell clones but instead give rise to secondarily responsive B cells. The existence of a distinct precursor cell subpopulation that is responsible for the generation of B cell memory is further evidenced by the distribution of variable region clonotypes among J11Dlo primary precursors, which resembles the clonotype patterns of secondary B cells, and by the accumulation of somatic mutations in their clonal progeny. 相似文献