全文获取类型
收费全文 | 308篇 |
免费 | 28篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 16篇 |
2020年 | 11篇 |
2019年 | 12篇 |
2018年 | 21篇 |
2017年 | 10篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 12篇 |
2013年 | 35篇 |
2012年 | 22篇 |
2011年 | 22篇 |
2010年 | 16篇 |
2009年 | 19篇 |
2008年 | 13篇 |
2007年 | 7篇 |
2006年 | 10篇 |
2005年 | 11篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有336条查询结果,搜索用时 15 毫秒
81.
Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally. 相似文献
82.
Iman Borazjani Mohsen Daghooghi 《Proceedings. Biological sciences / The Royal Society》2013,280(1756)
The tail (caudal fin) is one of the most prominent characteristics of fishes, and the analysis of the flow pattern it creates is fundamental to understanding how its motion generates locomotor forces. A mechanism that is known to greatly enhance locomotor forces in insect and bird flight is the leading edge vortex (LEV) reattachment, i.e. a vortex (separation bubble) that stays attached at the leading edge of a wing. However, this mechanism has not been reported in fish-like swimming probably owing to the overemphasis on the trailing wake, and the fact that the flow does not separate along the body of undulating swimmers. We provide, to our knowledge, the first evidence of the vortex reattachment at the leading edge of the fish tail using three-dimensional high-resolution numerical simulations of self-propelled virtual swimmers with different tail shapes. We show that at Strouhal numbers (a measure of lateral velocity to the axial velocity) at which most fish swim in nature (approx. 0.25) an attached LEV is formed, whereas at a higher Strouhal number of approximately 0.6 the LEV does not reattach. We show that the evolution of the LEV drastically alters the pressure distribution on the tail and the force it generates. We also show that the tail''s delta shape is not necessary for the LEV reattachment and fish-like kinematics is capable of stabilising the LEV. Our results suggest the need for a paradigm shift in fish-like swimming research to turn the focus from the trailing edge to the leading edge of the tail. 相似文献
83.
84.
Anghel A Mut-Vitcu B Savu L Marian C Seclaman E Iman R Neghina AM Dragulescu SI 《Genomic Medicine》2007,1(1-2):47-55
The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia
using a plasmid vector encoding the vascular endothelial growth factor (phVEGF165). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability
to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary
level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF
165
isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic
ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection
with 0.5 ml saline solution containing 1011 copies of VEGF
165
plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner
protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer
lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels. 相似文献
85.
Wei Bin Fang Iman Jokar An Zou Diana Lambert Prasanthi Dendukuri Nikki Cheng 《The Journal of biological chemistry》2012,287(43):36593-36608
Increased cell motility and survival are important hallmarks of metastatic tumor cells. However, the mechanisms that regulate the interplay between these cellular processes remain poorly understood. In these studies, we demonstrate that CCL2, a chemokine well known for regulating immune cell migration, plays an important role in signaling to breast cancer cells. We report that in a panel of mouse and human breast cancer cell lines CCL2 enhanced cell migration and survival associated with increased phosphorylation of Smad3 and p42/44MAPK proteins. The G protein-coupled receptor CCR2 was found to be elevated in breast cancers, correlating with CCL2 expression. RNA interference of CCR2 expression in breast cancer cells significantly inhibited CCL2-induced migration, survival, and phosphorylation of Smad3 and p42/44MAPK proteins. Disruption of Smad3 expression in mammary carcinoma cells blocked CCL2-induced cell survival and migration and partially reduced p42/44MAPK phosphorylation. Ablation of MAPK phosphorylation in Smad3-deficient cells with the MEK inhibitor U0126 further reduced cell survival but not migration. These data indicate that Smad3 signaling through MEK-p42/44MAPK regulates CCL2-induced cell motility and survival, whereas CCL2 induction of MEK-p42/44MAPK signaling independent of Smad3 functions as an alternative mechanism for cell survival. Furthermore, we show that CCL2-induced Smad3 signaling through MEK-p42/44MAPK regulates expression and activity of Rho GTPase to mediate CCL2-induced breast cancer cell motility and survival. With these studies, we characterize an important role for CCL2/CCR2 chemokine signaling in regulating the intrinsic relationships between breast cancer cell motility and survival with implications on the metastatic process. 相似文献
86.
Iman Sahly Eric Dufour Cataldo Schietroma Vincent Michel Amel Bahloul Isabelle Perfettini Elise Pepermans Amrit Estivalet Diane Carette Asadollah Aghaie Inga Ebermann Andrea Lelli Maria Iribarne Jean-Pierre Hardelin Dominique Weil José-Alain Sahel Aziz El-Amraoui Christine Petit 《The Journal of cell biology》2012,199(2):381-399
The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner–outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients. 相似文献
87.
88.
Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the analyses of Fgf6 (-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remained largely unclear. Recent reports support the concept that FGF6 has a dual function in muscle regeneration, stimulating myoblast proliferation/migration and muscle differentiation/hypertrophy in a dose-dependent manner. The alternative use of distinct signaling pathways recruiting either FGFR1 or FGFR4 might explain the dual role of FGF6 in myogenesis. A role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle has been also strongly suggested. The aim of this review is to summarize our knowledge on the involvement of FGF6 in myogenesis. 相似文献
89.
Iman Shabani Vahid Haddadi-Asl Farshad Babaeijandaghi Masoud Soleimani 《Biochemical and biophysical research communications》2009,382(1):129-4603
Nanofibrous scaffolds have been recently used in the field of tissue engineering because of their nano-size structure which promotes cell attachment, function, proliferation and infiltration. In this study, nanofibrous polyethersulfone (PES) scaffolds was prepared via electrospinning. The scaffolds were surface modified by plasma treatment and collagen grafting. The surface changes then investigated by contact angle measurements and FTIR-ATR. The results proved grafting of the collagen on nanofibers surface and increased hydrophilicity after plasma treatment and collagen grafting. The cell interaction study was done using stem cells because of their ability to differentiate to different kinds of cell lines. The cells had normal morphology on nanofibers and showed very high infiltration through collagen grafted PES nanofibers. This infiltration capability is very useful and needed to make 3D scaffolds in tissue engineering. 相似文献
90.
Mutations in the Hyperosmotic Stress-Responsive Mitochondrial BASIC AMINO ACID CARRIER2 Enhance Proline Accumulation in Arabidopsis 总被引:1,自引:0,他引:1