全文获取类型
收费全文 | 105篇 |
免费 | 19篇 |
出版年
2019年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 6篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 10篇 |
2006年 | 6篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 9篇 |
2002年 | 5篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有124条查询结果,搜索用时 31 毫秒
91.
Guiomar Pérez-Moreno Juan Cantizani Paula Sánchez-Carrasco Luis Miguel Ruiz-Pérez Jesús Martín Noureddine el Aouad Ignacio Pérez-Victoria José Rubén Tormo Víctor González-Menendez Ignacio González Nuria de Pedro Fernando Reyes Olga Genilloud Francisca Vicente Dolores González-Pacanowska 《PloS one》2016,11(1)
Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural products. 相似文献
92.
Phenological records as a complement to aerobiological data 总被引:1,自引:0,他引:1
Rafael Tormo Inmaculada Silva Ángela Gonzalo Alfonsa Moreno Remedios Pérez Santiago Fernández 《International journal of biometeorology》2011,55(1):51-65
Phenological studies in combination with aerobiological studies enable one to observe the relationship between the release
of pollen and its presence in the atmosphere. To obtain a suitable comparison between the daily variation of airborne pollen
concentrations and flowering, it is necessary for the level of accuracy of both sets of data to be as similar as possible.
To analyse the correlation between locally observed flowering data and pollen counts in pollen traps in order to set pollen
information forecasts, pollen was sampled using a Burkard volumetric pollen trap working continuously from May 1993. For the
phenological study we selected the main pollen sources of the six pollen types most abundant in our area: Cupressaceae, Platanus, Quercus, Plantago, Olea, and Poaceae with a total of 35 species. We selected seven sites to register flowering or pollination, two with semi-natural
vegetation, the rest being urban sites. The sites were visited weekly from March to June in 2007, and from January to June
in 2008 and 2009. Pollen shedding was checked at each visit, and recorded as the percentage of flowers or microsporangia in
that state. There was an association between flowering phenology and airborne pollen records for some of the pollen types
(Platanus, Quercus, Olea and Plantago). Nevertheless, for the other types (Cupressaceae and Poaceae) the flowering and airborne pollen peaks did not coincide,
with up to 1 week difference in phase. Some arguments are put forward in explanation of this phenomenon. Phenological studies
have shown that airborne pollen results from both local and distant sources, although the pollen peaks usually appear when
local sources are shedding the greatest amounts of pollen. Resuspension phenomena are probably more important than long-distance
transport in explaining the presence of airborne pollen outside the flowering period. This information could be used to improve
pollen forecasts. 相似文献
93.
Glithero A Tormo J Doering K Kojima M Jones EY Elliott T 《The Journal of biological chemistry》2006,281(18):12699-12704
In the absence of bound peptide ligands, major histocompatibility complex (MHC) class I molecules are unstable. In an attempt to determine the minimum requirement for peptide-dependent MHC class I stabilization, we have used short synthetic peptides derived from the Sendai virus nucleoprotein epitope (residues 324-332, 1FAPGNYPAL9) to promote its folding in vitro of H-2D(b). We found that H-2D(b) can be stabilized by the pentapeptide 5NYPAL9, which is equivalent to the C-terminal portion of the optimal nonapeptide and includes both the P5 and P9 anchor residues. We have crystallized the complex of the H-2D(b) molecule with the pentamer and determined the structure to show how a quasi-stable MHC class I molecule can be formed by occupancy of a single binding pocket in the peptide-binding groove. 相似文献
94.
Patricia Rodrigues Jessica Furriol Eduardo Tormo Sandra Ballester Ana Lluch Pilar Eroles 《Molecular and cellular biochemistry》2013,372(1-2):181-190
Arginine deprivation is a promising strategy for treating ASS-negative malignant tumors including melanoma. However, autophagy can potentially counteract the effectiveness of this treatment by acting as a pro-survival pathway. By combining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with arginine deprivation using ADI-PEG20 (pegylated arginine deiminase), we achieved enhanced apoptosis and accelerated cell death in melanoma cell lines. This implies a switch from autophagy to apoptosis. In our current investigation, we found that TRAIL could induce the cleavage of two key autophagic proteins, Beclin-1 and Atg5, in the combination treatment. Using specific inhibitors for individual caspases, we found that caspase-8 inhibitor could completely abolish the cleavage. Furthermore, caspase-8 inhibitor was able to fully reverse the enhanced cytotoxicity induced by TRAIL. Inhibitors for caspase-3, 6, 9, and 10 were able to block the cleavage of these two autophagic proteins to some extent and correspondingly rescue cells from the cytotoxicity of the combination of TRAIL and arginine deprivation. In contrast, calpain inhibitor could not prevent the cleavage of either Beclin-1 or Atg5, and was unable to prevent cell death. Overall, our data indicate that the cleavage of Beclin-1 and Atg5 by TRAIL-initiated caspase activation is one of the mechanisms that lead to the enhancement of the cytotoxicity in the combination treatment. 相似文献
95.
Differences in production of several extracellular virulence factors in clinical and food Aeromonas spp. strains 总被引:2,自引:1,他引:1
Carmen Pin M. Luisa Marín Dolores Selgas M. Luisa García J. Tormo Carmen Casas 《Journal of applied microbiology》1995,78(2):175-179
C. PIN, M.L. MARÍN, D. SELGAS, M.L. GARCÍA, J. TORMO AND C. CASAS. 1995. Production of several extracellular virulence factors (lipase, protease and haemolysin) was compared in 15 Aeromonas spp. isolated from faeces of patients with Aeromonas -associated gastroenteritis and 81 strains isolated from food. Strains from food did not show differences in production of these factors when compared with strains isolated from faeces. However, if strains were considered in relation to autoagglutination (AA) character, the AA+ differed from AA- strains in lipase and protease production. Supernatant fluids of AA+ food and human strains showed 2·5-fold more protease production than that observed in AA- strains. These two characteristics of certain Aeromonas strains could be related with the more virulent capacity. 相似文献
96.
Andreu I Cabedo N Tormo JR Bermejo A Mello R Cortes D 《Bioorganic & medicinal chemistry letters》2000,10(13):1491-1494
The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochondrial complexes I and III, and therefore it opens a new perspective with this series of compounds as they can be considered as new class of antitumor agents. 相似文献
97.
Gaffal E Schweichel D Tormo D Steitz J Lenz J Basner-Tschakarjan E Limmer A Tüting T 《European journal of cell biology》2007,86(11-12):817-826
The skin is an attractive target for antigen-specific vaccination. Particle bombardment of the epidermis with plasmid DNA using the gene gun results in antigen expression in keratinocytes of the epidermis leading to antigen presentation in the draining lymph nodes by migratory dendritic cells (DC). In order to better understand the role of the skin in stimulating antigen-specific CD8+cytotoxic T cells (CTL), we compared gene gun immunization with intracutaneous injections of antigen-transduced DC. A single intracutaneous injection of antigen-transduced DC was able to induce in vivo expansion of CD8+CTL specific for the model antigen chicken ovalbumin while four simultaneous shots with the gene gun were not effective. Antigen-transduced DC were much more efficient than particle bombardment of the epidermis in stimulating adoptively transferred TCR-transgenic CD8+CTL in the draining lymph nodes. Employing the novel technique of in vivo bioluminescence imaging, we demonstrated efficient gene transfer to the skin following gene gun bombardment and confirmed that a similar amount of antigen reached the lymph node when compared with injection of antigen-transduced DC. Our results suggest that direct transfection of the skin does not optimally reach and activate appropriate antigen-presenting DC. We believe that this reflects the immunological function of the epidermis which must balance immunity and tolerance to foreign antigens. Further investigations will have to address the role of Langerhans cells for the activation of cellular immunity in the skin. 相似文献
98.
Fernando Navarro-Mateu Ma José Tormo Diego Salmerón Gemma Vilagut Carmen Navarro Guadalupe Ruíz-Merino Teresa Escámez Javier Júdez Salvador Martínez Ron C. Kessler Jordi Alonso 《PloS one》2015,10(9)
Background
To describe the lifetime and 12-month prevalence, severity and age of onset distribution of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) disorders and to explore the association between socio-demographic variables and economic stressors with mental disorders during the economic crisis in the general population of Murcia (Spain).Methods and Findings
The PEGASUS-Murcia Project is a cross-sectional face-to-face interview survey of a representative sample of non-institutionalized adults in Murcia administered between June 2010 and May 2012. DSM-IV disorders were assessed by the Composite International Diagnostic Interview (CIDI 3.0). Main outcome measures were lifetime and 12-month prevalence of Anxiety, Mood, Impulse and Substance Disorders, Severity and Age of Onset. Sociodemographic variables and stressful economic life events during the preceding 12 months were entered as independent variables in a logistic regression analysis. A total of 2,621 participants (67.4% response rate) were interviewed, 54.5% female, mean age 48.6 years. Twelve-month prevalence (95%CI) of disorders: anxiety 9.7% (7.6–12.2), mood 6.6% (5.5–8.1), impulse 0.3% (0.1–1.2) and substance use 1.0% (0.4–2.4) disorders. Lifetime prevalence: anxiety 15.0% (12.3–18.1), mood 15.6% (13.5–18.1), impulse 2.4% (1.4–4.0) and substance use 8.3% (6.2–11.0) disorders. Severity among 12-month cases: serious 29.2% (20.8–39.4), moderate 35.6% (24.0–49.1) and mild severity 35.2% (29.5–41.5). Women were 3.7 and 2.5 times more likely than men to suffer 12-month anxiety and mood disorders, respectively. Substance use was more frequent among men. Younger age and lower income were associated with higher prevalence. Respondents exposed to multiple and recent economic stressors had the highest risk of anxiety disorders.Conclusions
Mental disorders in the adult population of Murcia during the economic crisis were more prevalent and serious than those in previous estimates for Spain. Prevalence was strongly associated with exposure to stressors related to the economic crisis. 相似文献99.
Sara W. Lazar Marta Almirn Antonio Tormo Roberto Kolter 《Journal of bacteriology》1998,180(21):5704-5711
SurA is a periplasmic peptidyl-prolyl isomerase required for the efficient folding of extracytoplasmic proteins. Although the surA gene had been identified in a screen for mutants that failed to survive in stationary phase, the role played by SurA in stationary-phase survival remained unknown. The results presented here demonstrate that the survival defect of surA mutants is due to their inability to grow at elevated pH in the absence of ςS. When cultures of Escherichia coli were grown in peptide-rich Luria-Bertani medium, the majority of the cells lost viability during the first two to three days of incubation in stationary phase as the pH rose to pH 9. At this time the surviving cells resumed growth. In cultures of surA rpoS double mutants the survivors lysed as they attempted to resume growth at the elevated pH. Cells lacking penicillin binding protein 3 and ςS had a survival defect similar to that of surA rpoS double mutants, suggesting that SurA foldase activity is important for the proper assembly of the cell wall-synthesizing apparatus. 相似文献
100.
Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition. 总被引:12,自引:0,他引:12 下载免费PDF全文
A Guarné J Tormo R Kirchweger D Pfistermueller I Fita T Skern 《The EMBO journal》1998,17(24):7469-7479
The leader protease of foot-and-mouth disease virus, as well as cleaving itself from the nascent viral polyprotein, disables host cell protein synthesis by specific proteolysis of a cellular protein: the eukaryotic initiation factor 4G (eIF4G). The crystal structure of the leader protease presented here comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C-terminal extension found intruding into the substrate-binding site of an adjacent molecule. Nevertheless, the relative disposition of this extension and the globular domain to each other supports intramolecular self-processing. The different sequences of the two substrates cleaved during viral replication, the viral polyprotein (at LysLeuLys/GlyAlaGly) and eIF4G (at AsnLeuGly/ArgThrThr), appear to be recognized by distinct features in a narrow, negatively charged groove traversing the active centre. The structure illustrates how the prototype papain fold has been adapted to the requirements of an RNA virus. Thus, the protein scaffold has been reduced to a minimum core domain, with the active site being modified to increase specificity. Furthermore, surface features have been developed which enable C-terminal self-processing from the viral polyprotein. 相似文献