全文获取类型
收费全文 | 140篇 |
免费 | 12篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 13篇 |
2012年 | 10篇 |
2011年 | 2篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 8篇 |
2007年 | 7篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1995年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1978年 | 1篇 |
1972年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有152条查询结果,搜索用时 281 毫秒
61.
62.
Biological adaptability has been proved to be analysable by means of the Maximum Entropy Formalism (MAXENT) in some cases
of non-interacting systems. This formalism is extended to the biomass statistical structures of populations exhibiting internal
interactions (i.e. predatorprey effects). 相似文献
63.
Juan Esteban Oyarzún Jonathan Lagos Mary Carmen Vázquez Cristian Valls Catalina De la Fuente María Isabel Yuseff Alejandra R. Alvarez Silvana Zanlungo 《生物化学与生物物理学报:疾病的分子基础》2019,1865(6):1076-1087
Lysosomes are dynamic organelles, which can fuse with a variety of targets and undergo constant regeneration. They can move along microtubules in a retrograde and anterograde fashion by using motor proteins, kinesin and dynein, being main players in extracellular secretion, intracellular components degradation and recycling. Moreover, lysosomes interact with other intracellular organelles to regulate their turnover, such as ER, mitochondria and peroxisomes.The correct localization of lysosomes is relevant in several physiological processes, including appropriate antigen presentation, neurotransmission and receptors modulation in neuronal synapsis, whereas hepatic lysosomes and autophagy are master regulators of nutrient homeostasis.Alterations in lysosome function due to mutation of genes encoding lysosomal proteins, soluble hydrolases as well as membrane proteins, lead to lysosomal storage diseases (LSDs). Lysosomes containing undegraded substrates are finally stacked and therefore miss positioned inside the cell, leading to lysosomal dysfunction, which impacts a wide range of cellular functions. 相似文献
64.
Marina Casanoves Zoel Salvadó Ángel González Cristina Valls 《Journal of biological education》2017,51(2):99-106
In this paper we discuss an activity through which students learn basic concepts in genetics by taking part in a police investigation game. The activity, which we have called Recal, immerses students in a scientific-based scenario in which they play a role of a scientific assessor. Players have to develop and use scientific reasoning and evidence-based decision-making to solve the given enigmas along the game. The activity aims to improve students’ knowledge of genetics and show them how genetic evidence can be applied in forensic science. The activity (known as ‘the Recal case’) uses a problem-based learning educational methodology. It is learner-centred and students play an active collaborative role. The methodology requires students to structure their knowledge, and develop their reasoning processes and self-directed learning skills. The activity has been developed for a range of audiences, including high school students, undergraduates engaged in pre-service teaching and adults of all ages. A case study has also been carried out with a group of 120 pre-service student teachers from the Universitat Rovira i Virgili (Tarragona, Spain) to check whether the coherence in the running of the game, whether its effectiveness as a learning activity and whether its dynamics and motivational aspects are acceptable. 相似文献
65.
66.
A microsatellite-based, gene-rich linkage map for the AA genome of Arachis (Fabaceae) 总被引:10,自引:0,他引:10
Moretzsohn MC Leoi L Proite K Guimarães PM Leal-Bertioli SC Gimenes MA Martins WS Valls JF Grattapaglia D Bertioli DJ 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(6):1060-1071
Cultivated peanut (Arachis hypogaea) is an important crop, widely grown in tropical and subtropical regions of the world. It is highly susceptible to several biotic and abiotic stresses to which wild species are resistant. As a first step towards the introgression of these resistance genes into cultivated peanut, a linkage map based on microsatellite markers was constructed, using an F2 population obtained from a cross between two diploid wild species with AA genome (A. duranensis and A. stenosperma). A total of 271 new microsatellite markers were developed in the present study from SSR-enriched genomic libraries, expressed sequence tags (ESTs), and by “data-mining” sequences available in GenBank. Of these, 66 were polymorphic for cultivated peanut. The 271 new markers plus another 162 published for peanut were screened against both progenitors and 204 of these (47.1%) were polymorphic, with 170 codominant and 34 dominant markers. The 80 codominant markers segregating 1:2:1 (P<0.05) were initially used to establish the linkage groups. Distorted and dominant markers were subsequently included in the map. The resulting linkage map consists of 11 linkage groups covering 1,230.89 cM of total map distance, with an average distance of 7.24 cM between markers. This is the first microsatellite-based map published for Arachis, and the first map based on sequences that are all currently publicly available. Because most markers used were derived from ESTs and genomic libraries made using methylation-sensitive restriction enzymes, about one-third of the mapped markers are genic. Linkage group ordering is being validated in other mapping populations, with the aim of constructing a transferable reference map for Arachis.Electronic supplementary material is available for this at 相似文献
67.
Morag E.?FergusonEmail author Andrew?Jarvis H. Tom?Stalker David E.?Williams Luigi?Guarino Jose F.M.?Valls Roy N.?Pittman Charles E.?Simpson Paula J.?Bramel 《Biodiversity and Conservation》2005,14(7):1777-1798
Geographic Information System (GIS) tools are applied to a comprehensive database of 3514 records of wild Arachis species to assist in the conservation and utilisation of the species by: (a) determining the distributional range of species and their abundance; (b) characterising species environments; (c) determining the geographical distribution of species richness; and (d) determining the extent to which species are associated with river basins. Distributional ranges, climatic variables and indices of endemism for each species are tabulated. A. duranensis Krapov. & W.C. Gregory, the most probable donor of the A genome to the cultivated peanut, is distributed in close proximity to both the proposed donor of the B genome, A. ipaënsis, and the closest wild relative of the cultigen, A. monticola Krapov. & Rigoni. This region in the eastern foothills of the Andes and the adjoining chaco regions of Argentina, Bolivia and Paraguay, is a key area for further exploration for wild Arachis. An area of particularly high species richness occurs in the State of Mato Grosso, close to the Gran Pantanal in southwest Brazil. Seventy-one percent of the species were found to have some degree of association with water catchment areas, although in most cases it was difficult to determine whether this was due to climatic adaptation reasons, restricted dispersal due to geocarpic habit, or the role of watercourses as a principal dispersal agent. In only two cases could climatic adaptation be eliminated as the reason for species distribution. 相似文献
68.
Isabel De Castro-Orós Rosa Solà Rosa María Valls Angel Brea Pilar Mozas Jose Puzo Miguel Pocoví 《PloS one》2016,11(3)
Background
Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial , there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms. NCT01562080Material and Methods
We sequenced the LDLR 3′ and 5′ untranslated regions (UTR) and the PCSK9 5′ UTR of 102 participants with moderate hypercholesterolemia in trial . In this trial, 50 individuals were treated with AP supplementation and the rest with placebo. NCT01562080Results
Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5′ UTR and rs14158 (c.*52G>A) in the LDLR 3′ UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004).Conclusions
Three polymorphisms in the 3′ UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5′ UTR region of PCSK9, c.−3383C>G and c.−2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP. 相似文献69.
2‐phenylethynesulphonamide (PFT‐μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP‐AUY922 in melanoma,by reducing GSH levels
下载免费PDF全文
![点击此处可从《Pigment cell & melanoma research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Andree Yeramian Alvar Vea Sandra Benítez Joan Ribera Mónica Domingo Maria Santacana Montserrat Martinez Oscar Maiques Joan Valls Xavier Dolcet Ramón Vilella Elisa Cabiscol Xavier Matias‐Guiu Rosa M. Marti 《Pigment cell & melanoma research》2016,29(3):352-371
Heat shock proteins (HSPs), are molecular chaperones that assist the proper folding of nascent proteins. This study aims to evaluate the antitumour effects of the hsp90 inhibitor NVP‐AUY922 in melanoma, both in vitro and in vivo. Our results show that NVP‐AUY922 inhibits melanoma cell growth in vitro, with down regulation of multiple signalling pathways involved in melanoma progression such as NF‐?B and MAPK/ERK. However, NVP‐AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP‐AUY922 and PFT‐μ, a dual inhibitor of both hsp70 and autophagy, induced a synergistic increase of cell death in vitro, and delayed tumour formation in A375M xenografts. PFT‐μ depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT‐μ further enhanced NVP‐AUY922‐induced cytotoxic effects. These data suggest a potential therapeutic role for NVP‐AUY922 used in combination with PFT‐μ, in melanoma. 相似文献
70.
N S Coll A Smidler M Puigvert C Popa M Valls J L Dangl 《Cell death and differentiation》2014,21(9):1399-1408
Autophagy is a major nutrient recycling mechanism in plants. However, its functional connection with programmed cell death (PCD) is a topic of active debate and remains not well understood. Our previous studies established the plant metacaspase AtMC1 as a positive regulator of pathogen-triggered PCD. Here, we explored the linkage between plant autophagy and AtMC1 function in the context of pathogen-triggered PCD and aging. We observed that autophagy acts as a positive regulator of pathogen-triggered PCD in a parallel pathway to AtMC1. In addition, we unveiled an additional, pro-survival homeostatic function of AtMC1 in aging plants that acts in parallel to a similar pro-survival function of autophagy. This novel pro-survival role of AtMC1 may be functionally related to its prodomain-mediated aggregate localization and potential clearance, in agreement with recent findings using the single budding yeast metacaspase YCA1. We propose a unifying model whereby autophagy and AtMC1 are part of parallel pathways, both positively regulating HR cell death in young plants, when these functions are not masked by the cumulative stresses of aging, and negatively regulating senescence in older plants.An emerging theme in cell death research is that cellular processes thought to be regulated by linear signaling pathways are, in fact, complex. Autophagy, initially considered merely a nutrient recycling mechanism necessary for cellular homeostasis, was recently shown to regulate cell death, mechanistically interacting with components that control apoptosis. Deficient autophagy can result in apoptosis1, 2, 3 and autophagy hyper-activation can also lead to programmed cell death (PCD).4 In addition, the pro-survival function of autophagy is mediated by apoptosis inhibition and apoptosis mediates autophagy, although this cross-regulation is not fully understood.5In plants, autophagy can also have both pro-survival and pro-death functions. Autophagy-deficient plants exhibit accelerated senescence,6, 7, 8 starvation-induced chlorosis,6, 7, 9 hypersensitivity to oxidative stress10 and endoplasmic reticulum stress.11 Further, autophagy-deficient plants cannot limit the spread of cell death after infection with tissue-destructive microbial infections.12, 13 The plant phytohormone salicylic acid (SA) mediates most of these phenotypes.8 Autophagy has an essential, pro-survival role in situations where there is an increasing load of damaged proteins and organelles that need to be eliminated, that is, during aging or stress. Autophagy has an opposing, pro-death role during developmentally regulated cell death14, 15 or during the pathogen-triggered hypersensitive response PCD (hereafter, HR) that occurs locally at the site of attempted pathogen attack.16, 17 The dual pro-death/pro-survival functions of plant autophagy remain a topic of active debate.Also under scrutiny are possible novel functions of caspases and caspase-like proteins as central regulators of pro-survival processes. Caspases were originally defined as executioners of PCD in animals, but increasing evidence indicates that several caspases have non-apoptotic regulatory roles in cellular differentiation, motility and in the mammalian immune system.18, 19, 20Yeast, protozoa and plants do not have canonical caspases, despite the occurrence of morphologically heterogeneous PCDs.21 More than a decade ago, distant caspase homologs termed metacaspases were identified in these organisms using structural homology searches.22 Metacaspases were classified into type I or type II metacaspases based on the presence or absence of an N-terminal prodomain, reminiscent of the classification in animals into initiator/inflammatory or executioner caspases, respectively. Despite the architectural analogy between caspases and metacaspases, differences in their structure, function, activation and mode of action exist.23, 24, 25Metacaspases mediate PCD in yeast,26, 27, 28, 29, 30, 31 leishmania,32, 33 trypanosoma34 and plants.24 We demonstrated that two type I metacaspases, AtMC1 and AtMC2, antagonistically regulate HR in Arabidopsis thaliana.35 Our work showed that AtMC1 is a positive regulator of HR and that this function is mediated by its catalytic activity and negatively regulated by the AtMC1 N-terminal prodomain. AtMC2 antagonizes AtMC1-mediated HR.Besides AtMC2, new examples of metacaspases with a pro-life/non-PCD role are emerging. Protozoan metacaspases are involved in cell cycle dynamics34, 36, 37, 38 and cell proliferation.39 The yeast metacaspase Yca1 alters cell cycle dynamics40 and interestingly, is required for clearance of insoluble protein aggregates, thus contributing to yeast fitness.41Here, we explore the linkage between plant autophagy and AtMC1 function in the context of pathogen-triggered HR and aging. Our data support a model wherein autophagy and AtMC1 are part of parallel pathways, both positively regulating HR cell death in young plants and negatively regulating senescence in older plants. 相似文献