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1.
Biomechanics of chelipeds in some decapod crustaceans 总被引:2,自引:0,他引:2
The major chelipeds of five species of decapod crustaceans were studied with reference to lever system mechanical advantage, pattern of occlusive geometry, and force/pressure developed during cheliped closure by intact animals. Every cheliped type was found to possess a linear array of two to four distinctive regions of occlusion. The factors responsible for the differences in occlusive design are discussed. It is suggested that crustacean major chelipeds must be regarded as regionally-specialized, multifunctional appendages. 相似文献
2.
Laminin (LN), an extracellular matrix component, is a key factor in promoting axonal regeneration, coordinately regulating growth in conjunction with trophic signals provided by the neurotrophins, including nerve growth factor (NGF). This study investigated potential interactions between the LN and NGF-mediated signaling pathways in PC12 cells and primary neurons. Neurite outgrowth stimulated by NGF was enhanced on a LN substrate. Western blot analysis of pertinent signal transduction components revealed both enhanced phosphorylation of early signaling intermediates upon co-stimulation, and a LN-induced down-regulation of p75NTR which could be prevented by the addition of integrin inhibitory arginine-glycine-aspartate (RGD) peptides. This p75NTR down-regulation was associated with a LN-mediated up-regulation of PTEN and resulted in a decrease in Rho activity. Studies using over-expression or siRNA-mediated knock-down of PTEN demonstrate a consistent inverse relationship with p75NTR, and the over-expression of p75NTR impaired neurite outgrowth on a LN substrate, as well as resulting in sustained activation of Rho which is inhibitory to neurite outgrowth. p75NTR is documented for its role in the transduction of inhibitory myelin-derived signals, and our results point to extracellular matrix regulation of p75NTR as a potential mechanism to ameliorate inhibitory signaling leading to optimized neurite outgrowth. 相似文献
3.
Karuppanan Muthusamy Kathir Li Gao Dakshinamurthy Rajalingam Sherri Brixey Dan Davis Igor Prudovsky 《生物化学与生物物理学报:生物膜》2010,1798(2):297-302
Human fibroblast growth factor (hFGF-1) is a ∼ 17 kDa heparin binding cytokine. It lacks the conventional hydrophobic N-terminal signal sequence and is secreted through non-classical secretion routes. Under stress, hFGF-1 is released as a multiprotein complex consisting of hFGF-1, S100A13 (a calcium binding protein), and p40 synaptotagmin (Syt1). Copper (Cu2+) is shown to be required for the formation of the multiprotein hFGF-1 release complex (Landriscina et al. ,2001; Di Serio et al., 2008). Syt1, containing the lipid binding C2B domain, is believed to play an important role in the eventual export of the hFGF-1 across the lipid bilayer. In this study, we characterize Cu2+ and lipid interactions of the C2B domain of Syt1 using multidimensional NMR spectroscopy. The results highlight how Cu2+ appears to stabilize the protein bound to pS vesicles. Cu2+ and lipid binding interface mapped using 2D 1H-15N heteronuclear single quantum coherence experiments reveal that residues in β-strand I contributes to the unique Cu2+ binding site in the C2B domain. In the absence of metal ions, residues located in Loop II and β-strand IV contribute to binding to unilamelar pS vesicles. In the presence of Cu2+, additional residues located in Loops I and III appear to stabilize the protein-lipid interactions. The results of this study provide valuable information towards understanding the molecular mechanism of the Cu2+-induced non-classical secretion of hFGF-1. 相似文献
4.
5.
Asadur Tchekmedyian Christopher I. Amos Sherri J. Bale Dakai Zhu Stefan Arold Joaquin Berrueta Natalie Nabon Thomas McGarrity 《PloS one》2013,8(11)
Background
Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients.Methods
Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed.Results and discussion
25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000.Conclusion
The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation. 相似文献6.
Gizem Kalay Joel Atallah Noemie C. Sierra Austin M. Tang Amanda E. Crofton Mohan K. Murugesan Sherri Wykoff-Clary Susan E. Lott 《Evolution; international journal of organic evolution》2020,74(7):1409-1422
Many developmental traits that are critical to the survival of the organism are also robust. These robust traits are resistant to phenotypic change in the face of variation. This presents a challenge to evolution. In this article, we asked whether and how a well-established robust trait, Drosophila segment patterning, changed over the evolutionary history of the genus. We compared segment position scaled to body length at the first-instar larval stage among 12 Drosophila species. We found that relative segment position has changed many times across the phylogeny. Changes were frequent, but primarily small in magnitude. Phylogenetic analysis demonstrated that rates of change in segment position are variable along the Drosophila phylogenetic tree, and that these changes can occur in short evolutionary timescales. Correlation between position shifts of segments decreased as the distance between two segments increased, suggesting local control of segment position. The posterior-most abdominal segment showed the highest magnitude of change on average, had the highest rate of evolution between species, and appeared to be evolving more independently as compared to the rest of the segments. This segment was exceptionally elongated in the cactophilic species in our dataset, raising questions as to whether this change may be adaptive. 相似文献
7.
Short-Term Effects of Traditional and Alternative Community Interventions to Address Food Insecurity
Background
Despite the effects of food insecurity on health are well documented, clear governmental policies to face food insecurity do not exist in western countries. In Canada, interventions to face food insecurity are developed at the community level and can be categorized into two basic strategies: those providing an immediate response to the need for food, defined “traditional” and those targeting the improvement of participants’ social cohesion, capabilities and management of their own nutrition, defined “alternative”.Objective
The objective of this study was to evaluate the effects of food insecurity interventions on food security status and perceived health of participants.Design
This was a longitudinal multilevel study implemented in Montreal, Quebec, Canada. Participants were recruited in a two-stage cluster sampling frame. Clustering units were community organizations working on food insecurity; units of analysis were participants in community food security interventions. A total of 450 participants were interviewed at the beginning and after 9 months of participation in traditional or alternative food security interventions. Food security and perceived health were investigated as dependent variables. Differences overtime were assessed through multilevel regression models.Results
Participants in traditional interventions lowered their food insecurity at follow-up. Decreases among participants in alternative interventions were not statistically significant. Participants in traditional interventions also improved physical (B coefficient 3.00, CI 95% 0.42–5.59) and mental health (B coefficient 6.25, CI 95% 4.15–8.35).Conclusions
Our results challenge the widely held view suggesting the ineffectiveness of traditional interventions in the short term. Although effects may be intervention-dependent, food banks decreased food insecurity and, in so doing, positively affected perceived health. Although study findings demonstrate that food banks offer short term reprise from the effects of food insecurity, the question as to whether food banks are the most appropriate solution to food insecurity still needs to be addressed. 相似文献8.
David B Gilberto Maria S Michener Brad E Smith Peter J Szczerba Marie A Holahan Tasha L Gray Sherri L Motzel 《Comparative medicine》2022,72(1):45
More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus macaques using this approach. Our experience enables us to provide up-to-date information regarding the model, including refinements to our implant design, reductions in maintenance, and new procedures for dealing with contamination. The results of our experiences have reduced the number of surgeries required and helped to increase the longevity of the implant, with some functioning for more than 18 y. Building on our success in rhesus macaques, we attempted to develop similar animal models in the African green monkeys and dogs but have been unable to develop reliable chronic models for CSF collection in these species.Abbreviation: CMP, cisterna magna port; CSF, cerebrospinal fluidCerebrospinal (CSF) biomarkers and pharmacokinetics are reliable tools for monitoring the therapeutic effect of compounds used for the treatment of various neurodegenerative diseases. CSF can be collected by using several methods, including lumbar and cisterna magna punctures or implanted devices.3,6,8,9,11-13 Each method has its own specific challenges but no matter which technique is used, performing CSF collections safely is imperative to avoiding risks to the animals and to providing the best CSF samples for analysis.1 To support our research focus on neurocognitive disorders (including Alzheimer disease, Parkinson disease, and sleep disorders), we developed an NHP model of chronic CSF collection (the cisterna magna port [CMP] model) more than 20 y ago.4 This model allows safe, repeatable and reliable collections of CSF samples from the cisterna magna in conscious rhesus macaques (Macaca mulatta). The information summarized herein updates this animal model since its introduction in 2003 and reflects our 18 additional years of experience with it. We also provide information regarding our attempts to develop CMP models in African green monkeys and dogs. We recommend that readers review the 2003 article for further information and understanding of the CMP model.4 相似文献
9.
N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase activity of Galphai 总被引:1,自引:0,他引:1
Ippolito DL Temkin PA Rogalski SL Chavkin C 《The Journal of biological chemistry》2002,277(36):32692-32696
trkB activation results in tyrosine phosphorylation of N-terminal Kir3 residues, decreasing channel activation. To determine the mechanism of this effect, we reconstituted Kir3, trkB, and the mu opioid receptor in Xenopus oocytes. Activation of trkB by BDNF (brain-derived neurotrophic factor) accelerated Kir3 deactivation following termination of mu opioid receptor signaling. Similarly, overexpression of RGS4, a GTPase-activating protein (GAP), accelerated Kir3 deactivation. Blocking GTPase activity with GTPgammaS also prevented Kir3 deactivation, and the GTPgammaS effect was not reversed by BDNF treatment. These results suggest that BDNF treatment did not reduce Kir3 affinity for Gbetagamma but rather acted to accelerate GTPase activity, like RGS4. Tyrosine phosphatase inhibition by peroxyvanadate pretreatment reversibly mimicked the BDNF/trkB effect, indicating that tyrosine phosphorylation of Kir3 may have caused the GTPase acceleration. Tyrosine to phenylalanine substitution in the N-terminal domain of Kir3.4 blocked the BDNF effect, supporting the hypothesis that phosphorylation of these tyrosines was responsible. Like other GAPs, Kir3.4 contains a tyrosine-arginine-glutamine motif that is thought to function by interacting with G protein catalytic domains to facilitate GTP hydrolysis. These data suggest that the N-terminal tyrosine hydroxyls in Kir3 normally mask the GAP activity and that modification by phosphorylation or phenylalanine substitution reveals the GAP domain. Thus, BDNF activation of trkB could inhibit Kir3 by facilitating channel deactivation. 相似文献
10.
Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome 总被引:11,自引:0,他引:11 下载免费PDF全文
Richard G Rouan F Willoughby CE Brown N Chung P Ryynänen M Jabs EW Bale SJ DiGiovanna JJ Uitto J Russell L 《American journal of human genetics》2002,70(5):1341-1348
Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we provide compelling evidence that KID is caused by heterozygous missense mutations in the connexin-26 gene, GJB2. In each of 10 patients with KID, we identified a point mutation leading to substitution of conserved residues in the cytoplasmic amino terminus or first extracellular domain of Cx26. One of these mutations was detected in six unrelated sporadic case subjects and also segregated in one family with vertical transmission of KID. These results indicate the presence of a common, recurrent mutation and establish its autosomal dominant nature. Cx26 and the closely related Cx30 showed differential expression in epidermal, adnexal, and corneal epithelia but were not significantly altered in lesional skin. However, mutant Cx26 was incapable of inducing intercellular coupling in vitro, which indicates its functional impairment. Our data reveal striking genotype-phenotype correlations and demonstrate that dominant GJB2 mutations can disturb the gap junction system of one or several ectodermal epithelia, thereby producing multiple phenotypes: nonsyndromic SNHL, syndromic SNHL with palmoplantar keratoderma, and KID. Decreased host defense and increased carcinogenic potential in KID illustrate that gap junction communication plays not only a crucial role in epithelial homeostasis and differentiation but also in immune response and epidermal carcinogenesis. 相似文献