全文获取类型
收费全文 | 84篇 |
免费 | 9篇 |
出版年
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 6篇 |
2011年 | 7篇 |
2010年 | 3篇 |
2008年 | 1篇 |
2007年 | 8篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 6篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1971年 | 1篇 |
1944年 | 1篇 |
排序方式: 共有93条查询结果,搜索用时 31 毫秒
1.
Weiwei Luo Cheng-han Yu Zi Zhao Lieu Jun Allard Alex Mogilner Michael P. Sheetz Alexander D. Bershadsky 《The Journal of cell biology》2013,202(7):1057-1073
A ctin filaments, with the aid of multiple accessory proteins, self-assemble into a variety of network patterns. We studied the organization and dynamics of the actin network in nonadhesive regions of cells bridging fibronectin-coated adhesive strips. The network was formed by actin nodes associated with and linked by myosin II and containing the formin disheveled-associated activator of morphogenesis 1 (DAAM1) and the cross-linker filamin A (FlnA). After Latrunculin A (LatA) addition, actin nodes appeared to be more prominent and demonstrated drift-diffusion motion. Superresolution microscopy revealed that, in untreated cells, DAAM1 formed patches with a similar spatial arrangement to the actin nodes. Node movement (diffusion coefficient and velocity) in LatA-treated cells was dependent on the level and activity of myosin IIA, DAAM1, and FlnA. Based on our results, we developed a computational model of the dynamic formin-filamin-actin asters that can self-organize into a contractile actomyosin network. We suggest that such networks are critical for connecting distant parts of the cell to maintain the mechanical coherence of the cytoplasm. 相似文献
2.
Peishen Zhao TinaMarie Lieu Nicholas Barlow Matthew Metcalf Nicholas Veldhuis Dane D. Jensen Martina Kocan Silvia Sostegni Silke Haerteis Vera Baraznenok Ian Henderson Erik Lindstr?m Raquel Guerrero-Alba Eduardo E. Valdez-Morales Wolfgang Liedtke Peter McIntyre Stephen J. Vanner Christoph Korbmacher Nigel W. Bunnett 《The Journal of biological chemistry》2014,289(52):35858
3.
Identification of Isopentenol Biosynthetic Genes from Bacillus subtilis by a Screening Method Based on Isoprenoid Precursor Toxicity 总被引:2,自引:0,他引:2 下载免费PDF全文
Sydnor T. Withers Shayin S. Gottlieb Bonny Lieu Jack D. Newman Jay D. Keasling 《Applied microbiology》2007,73(19):6277-6283
We have developed a novel method to clone terpene synthase genes. This method relies on the inherent toxicity of the prenyl diphosphate precursors to terpenes, which resulted in a reduced-growth phenotype. When these precursors were consumed by a terpene synthase, normal growth was restored. We have demonstrated that this method is capable of enriching a population of engineered Escherichia coli for those clones that express the sesquiterpene-producing amorphadiene synthase. In addition, we enriched a library of genomic DNA from the isoprene-producing bacterium Bacillus subtilis strain 6051 in E. coli engineered to produce elevated levels of isopentenyl diphosphate and dimethylallyl diphosphate. The selection resulted in the discovery of two genes (yhfR and nudF) whose protein products acted directly on the prenyl diphosphate precursors and produced isopentenol. Expression of nudF in E. coli engineered with the mevalonate-based isopentenyl pyrophosphate biosynthetic pathway resulted in the production of isopentenol. 相似文献
4.
OBJECTIVES: Because the trigone is a unique region in the caudal bladder with a higher risk of neoplasia, we hypothesized that this area would have a high proportion of progenitor cells. As yet there is no marker nor methodology to specifically isolate urothelial stem cells, and thus demonstrate multi-potential differentiation and self-renewal. Here, our goal was to evaluate the distribution of progenitor cells that carry two general major attributes of stem cells: clonogenicity and proliferative capacity. MATERIALS AND METHODS: The bladders of Fisher rats were divided into caudal and cephalic segments and primary cultures were established from the harvested urothelial cells. RESULTS: We found that colony-forming efficiency was almost 2-fold higher for cells from the caudal bladder compared to the cephalic bladder. Doubling time was significantly faster for cells harvested from the caudal bladder at initial plating. This suggested that the caudal bladder harbours a higher density of urothelial progenitor cells. With passage to p4, the differences between the upper and lower bladder were lost, suggesting selection of proliferative cells with serial passage. Based on Ki-67 staining, there was no geographical difference in cell proliferation under normal homeostatic in vivo conditions. CONCLUSIONS: These results demonstrate geographical sequestration of urothelial progenitor cells to the area of the bladder that encompasses the bladder neck and trigone, which may be a factor in pathological disparities between the trigone and remaining bladder. 相似文献
5.
6.
Altering the expression kinetics of VP5 results in altered virulence and pathogenesis of herpes simplex virus type 1 in mice 下载免费PDF全文
While many herpes simplex virus (HSV) structural proteins are expressed with strict-late kinetics, the HSV virion protein 5 (VP5) is expressed as a "leaky-late" protein, such that appreciable amounts of VP5 are made prior to DNA replication. Our goal has been to determine if leaky-late expression of VP5 is a requirement for a normal HSV infection. It had been shown previously that recombinant viruses in which the VP5 promoter was replaced with promoters of other kinetic classes (including a strict late promoter) exhibited no alterations in replication kinetics or virus yields in vitro. In contrast, here we report that alterations in pathogenesis were observed when these recombinants were analyzed by experimental infection of mice. Following intracranial inoculation, a recombinant expressing VP5 from a strict-late promoter (U(L)38) exhibited an increased 50% lethal dose and a 10-fold decrease in virus yields in the central nervous system, while a recombinant expressing VP5 from an early (dUTPase) or another leaky-late (VP16) promoter exhibited wild-type neurovirulence. Moreover, following infection of the footpad, changing the expression kinetics of VP5 from leaky-late to strict-late resulted in 100-fold-less virus in the spinal ganglia during the acute infection than produced by either the parent virus or the rescued virus. These data indicate that the precise timing of appearance of the major capsid protein plays a role in the pathogenesis of HSV infections and that changing the expression kinetics has different effects in different cell types and tissues. 相似文献
7.
The depolarizing membrane ionic current I
h (also known as I
f, “f” for funny), encoded by the hyperpolarization-activated cyclic-nucleotide-modulated (HCN1-4) channel gene family, was
first discovered in the heart over 25 years ago. Later, I
h was also found in neurons, retina, and taste buds. HCN channels structurally resemble voltage-gated K+ (Kv) channels but the molecular features underlying their opposite gating behaviors (activation by hyperpolarization rather
than depolarization) and non-selective permeation profiles (≥25 times less selective for K+ than Kv channels) remain largely unknown. Although I
h has been functionally linked to biological processes from the autonomous beating of the heart to pain transmission, the underlying
mechanistic actions remain largely inferential and, indeed, somewhat controversial due to the slow kinetics and negative operating
voltage range relative to those of the bioelectrical events involved (e.g., cardiac pacing). This article reviews the current
state of our knowledge in the structure-function properties of HCN channels in the context of their physiological functions
and potential HCN-based therapies via bioengineering. 相似文献
8.
Previous studies in man have shown that T cells with suppressor activity were mainly found among a subset bearing Fc receptors for IgG (Tγ). Recently, we found that virus-induced cytotoxic effector cells were also found predominantly among Tγ cells. In the present studies, we present evidence that similar, possibly overlapping T-cell populations can mediate both suppressor and cytotoxic activities when sensitized in vitro with virus-infected cells. In fact, both activities are found within the positively selected Tγ subset, but not in the Tγ-depleted population; both activities are abolished by irradiation but not by treatment with mitomycin C; a 1-hr exposition to theophylline at the onset of sensitization enhances both cytotoxic and suppressor activities. The data suggest that development of antiviral cell-mediated immune responses in vivo may also be accompanied by a concurrent induction of nonspecific suppressor cells. Such suppressor activity may play a role in the depressed cellular immune responsiveness which is associated with several systemic virus infections. 相似文献
9.
Wu-Nan Wen Tai-Lin Lieu Huei-Jane Chang Sheng Wang Wuu Mei-Ling Yau K. Y. Jan 《Human genetics》1981,59(3):201-203
Summary A significantly higher frequency of baseline sister chromatid exchange (SCE) was found in the cultured lymphocytes of 13 Blackfoot disease patients (BFP) in comparison with that of healthy persons (HP). Twelve of these BFP consumed well water containing a high concentration of arsenic for 15 years or longer and had switched to drinking tap water 12 years before the time of this study. Sodium arsenite was found to be effective in increasing the SCE frequency and delaying the cell growth of the lymphocytes from both BFP and HP. However, the SCE increment induced by sodium arsenite as well as the progression of the cell divisions in the cultured lymphocytes showed no significant difference between BFP and HP. 相似文献
10.
Anita P. Kuan Winston Chamberlain Susan Malkiel Hsiao D. Lieu Stephen M. Factor B. Diamond Brian L. Kotzin 《Immunogenetics》1999,49(2):79-85
Autoimmune disease involves both the development of autoreactivity and the expression of organ damage, and susceptibility
is genetically complex. We recently reported that in autoimmune myocarditis susceptibility to antibody-mediated cardiac injury
is strain specific. DBA/2 mice develop myocarditis following administration of myosin-specific antibody, while BALB/c mice
do not. This susceptibility appears to be controlled by expression of myosin in the myocardial extracellular matrix. CByD2F1
mice are both resistant to induction of myocarditis and do not demonstrate extracellular myosin, indicating a recessive genetic
component to these traits. A backcross analysis of susceptibility using DBA/2×CByD2F1 mice revealed a locus on chromosome
12 that is strongly linked with myocarditis. In male mice there was a second region on chromosome 1 that also contributes
to disease susceptibility. However, genetic susceptibility in both female and male mice was genetically complex. This study
demonstrates that the genetic basis of tissue injury can be analyzed separately from the genetic basis of autoreactivity.
Future studies will determine whether the genetic factors identified in this study are also involved in susceptibility to
rheumatic fever.
Received: 18 May 1998 / Revised: 3 July 1998 相似文献