全文获取类型
收费全文 | 157篇 |
免费 | 14篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 6篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 10篇 |
2016年 | 11篇 |
2015年 | 15篇 |
2014年 | 18篇 |
2013年 | 13篇 |
2012年 | 11篇 |
2011年 | 16篇 |
2010年 | 5篇 |
2009年 | 7篇 |
2008年 | 7篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1984年 | 1篇 |
1977年 | 2篇 |
排序方式: 共有171条查询结果,搜索用时 171 毫秒
61.
Raymond Poon Saeid Amini Nik Jessica Ahn Laura Slade Benjamin A Alman 《BMC cell biology》2009,10(1):38-10
Background
β-catenin and transforming growth factor β signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor β is partially mediated by β-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of β-catenin and its interaction with transforming growth factor β in cell motility and the induction of collagen lattice contraction. 相似文献62.
Kah Keng Wong Lewis H. Mervin Angelica Mazzolari Andreas Bender Nik Soriani Yaacob 《Journal of plant biochemistry and biotechnology.》2017,26(4):451-466
Bioactive sub-fractions from the tropical herbal plant Strobilanthes crispus (S. crispus) has been shown to induce apoptosis of breast cancer cells in vitro and reduce tumor size in vivo by our earlier studies. We have recently isolated five major compounds from S. crispus sub-fraction, namely lutein, β-sitosterol, campesterol, stigmasterol and pheophytin a. In this study, we set out to investigate each compound’s protein targets and mechanism of action through prediction of protein targets via a ligand-based target prediction protocol, Prediction IncluDinG INactives, and radioligand binding assays. The three phytosterol molecules (β-sitosterol, campesterol, stigmasterol) showed enrichment of hormone signaling GO terms [average ratio (AR) <0.01], while the SMAD signaling pathway was associated with pheophytin a (AR < 0.01). GO terms associated with retinoic acid receptor (RAR) and retinoid X receptor (RXR) were distinctly represented by protein targets of lutein (AR < 0.01). All members of the RAR/RXR family of proteins were predicted to be targeted by lutein, a feature that was not present in the other four S. crispus-derived compounds. Radioligand binding assay in vitro validated that lutein showed higher binding affinity with RXRα (IC50: 5.74 µM; Ki: 4.55 µM) than RARα (IC50: 25.1 µM; Ki: 14 µM). Molecular docking analysis demonstrated that lutein could occupy a large hydrophobic cavity of the hRXRα-LBP crystal structure mainly through hydrophobic interactions with leucine and isoleucine residues, and also hydrogen bond between a hydroxyl group of lutein with Glu239. Our findings suggest that lutein-RXRα interaction might play a role in the anti-breast cancer effects rendered by S. crispus. 相似文献
63.
Normal Skeletal Development of Mice Lacking Matrilin 1: Redundant Function of Matrilins in Cartilage? 下载免费PDF全文
Attila Aszdi John F. Bateman Emilio Hirsch Mria Baranyi Ernst B. Hunziker Nik Hauser Zsuzsa Bsze Reinhard Fssler 《Molecular and cellular biology》1999,19(11):7841-7845
Matrilin 1, or cartilage matrix protein, is a member of a novel family of extracellular matrix proteins. To date, four members of the family have been identified, but their biological role is unknown. Matrilin 1 and matrilin 3 are expressed in cartilage, while matrilin 2 and matrilin 4 are present in many tissues. Here we describe the generation and analysis of mice carrying a null mutation in the Crtm gene encoding matrilin 1. Anatomical and histological studies demonstrated normal development of homozygous mutant mice. Northern blot and biochemical analyses show no compensatory up-regulation of matrilin 2 or 3 in the cartilage of knockout mice. Although matrilin 1 interacts with the collagen II and aggrecan networks of cartilage, suggesting that it may play a role in cartilage tissue organization, studies of collagen extractability indicated that collagen fibril maturation and covalent cross-linking were unaffected by the absence of matrilin 1. Ultrastructural analysis did not reveal any abnormalities of matrix organization. These data suggest that matrilin 1 is not critically required for cartilage structure and function and that matrilin 1 and matrilin 3 may have functionally redundant roles. 相似文献
64.
Nik J. Cunniffe Nick P. Taylor Frdric M. Hamelin Michael J. Jeger 《PLoS computational biology》2021,17(12)
Many plant viruses are transmitted by insect vectors. Transmission can be described as persistent or non-persistent depending on rates of acquisition, retention, and inoculation of virus. Much experimental evidence has accumulated indicating vectors can prefer to settle and/or feed on infected versus noninfected host plants. For persistent transmission, vector preference can also be conditional, depending on the vector’s own infection status. Since viruses can alter host plant quality as a resource for feeding, infection potentially also affects vector population dynamics. Here we use mathematical modelling to develop a theoretical framework addressing the effects of vector preferences for landing, settling and feeding–as well as potential effects of infection on vector population density–on plant virus epidemics. We explore the consequences of preferences that depend on the host (infected or healthy) and vector (viruliferous or nonviruliferous) phenotypes, and how this is affected by the form of transmission, persistent or non-persistent. We show how different components of vector preference have characteristic effects on both the basic reproduction number and the final incidence of disease. We also show how vector preference can induce bistability, in which the virus is able to persist even when it cannot invade from very low densities. Feedbacks between plant infection status, vector population dynamics and virus transmission potentially lead to very complex dynamics, including sustained oscillations. Our work is supported by an interactive interface https://plantdiseasevectorpreference.herokuapp.com/. Our model reiterates the importance of coupling virus infection to vector behaviour, life history and population dynamics to fully understand plant virus epidemics. 相似文献
65.
Bernard C. Broughton Nik Barbet Johanne Murray Felicity Z. Watts Marcel H. M. Koken Alan R. Lehmann Antony M. Carr 《Molecular & general genetics : MGG》1991,228(3):470-472
Summary Ten DNA repair (rad) genes from the fission yeast, Schizosaccharomyces pombe were mapped to the 17 NotI fragments of the three chromosomes. Nine of the genes map to chromosome I, but there is no evidence for significant clustering. 相似文献
66.
Summary Growth of and of some lambdoid phages is considerably inhibited on strain 3057 derived from E. coli 15T-. Mutants of which overcome this inhibition map in gene N. Some of these hty mutants are temperature sensitive for growth on E. coli K12. Thus plating of on strain 3057 allows one to isolate temperature sensitive N mutants. The hty mutants produce less than normal N activity as judged by their low efficiency of plating on a nus
- host and by the extended latent period of some of them on normal hosts. The inability of strain 3057 to propagate can be at least partially reversed by addition of thymidine to the medium and the growth difference between hty and in 3057 increases with decreasing thymidine concentration. The amount of DNA produced by in 3057 at low thymidine concentration is lower than that produced by hty under the same conditions. Only a small percentage of the DNA produced by in 3057 is packaged into viable phage particles. This suggests that not only produces less DNA in 3057 than hty but that an important part of the DNA in 3057 is in a form which can not be packaged or which is noninfective for other reasons. A hypothesis is discussed that hty mutations enable to grow on E. coli 15T- at low thymidine concentration because they lead to reduction in the number of single strand nicks in the DNA by reducing the intracellular endonuclease activity. Under permissive conditions conditional lethal N mutants are favored for growth on 3057 over N
+ which confirms the idea that N activity or the activity of a gene under N control interferes with growth in 3057 at low thymidine concentration. 相似文献
67.
Health care professionals today struggle to establish strategic directions for the future, in part because of the continuing uncertainties engendered by innovations in the diagnosis and treatment of disease. Emerging technologies such as genetics and information technology pose acute challenges for healthcare professionals in respect to questions of service provision, organizational change and the meaning of health and illness. This paper contrasts two areas of health technology development in the UK, genetics diagnostics and telemedicine, and asks how diverse actors attempt to manage innovation. Several key dimensions are elaborated for understanding the future-orientated dynamics at work in emerging health innovation areas. In so doing, this paper examines how the unique attributes of both areas entail differing opportunities and constraints for mobilizing 'the future'. 相似文献
68.
Victoria Gillan Kirsty Maitland Gillian McCormack Nik A.I.I. Nik Him Eileen Devaney 《International journal for parasitology》2009,39(10):1071-1081
Heat shock protein 90 (Hsp-90) is a highly conserved essential protein in eukaryotes. Here we describe the molecular characterisation of hsp-90 from three nematodes, the free-living Caenorhabditis elegans (Ce) and the parasitic worms Brugia pahangi (Bp) and Haemonchus contortus (Hc). These molecules were functionally characterised by rescue of a Ce-daf-21 (hsp-90) null mutant. Our results show a gradient of rescue: the C. elegans endogenous gene provided full rescue of the daf-21 mutant, while Hc-hsp-90 provided partial rescue. In contrast, no rescue could be obtained using a variety of Bp-hsp-90 constructs, despite the fact that Bp-hsp-90 was transcribed and translated in the mutant worms. daf-21 RNA interference (RNAi) experiments were carried out to determine whether knock-down of the endogenous daf-21 mRNA in N2 worms could be complemented by expression of either parasite gene. However neither parasite gene could rescue the daf-21 (RNAi) phenotypes. These results indicate that factors other than the level of sequence identity are important for determining whether parasite genes can functionally complement in C. elegans. 相似文献
69.
Nik AIIN Him Victoria Gillan Richard D Emes Kirsty Maitland Eileen Devaney 《BMC evolutionary biology》2009,9(1):254