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41.
42.
Gonzalo E. Yevenes Gustavo Moraga-Cid Ariel Avila Leonardo Guzmán Maximiliano Figueroa Robert W. Peoples Luis G. Aguayo 《The Journal of biological chemistry》2010,285(39):30203-30213
It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two ligand-gated ion receptor members, the GlyR adult α1 and embryonic α2 subunits, can be modified through selective mutations that rescued or impaired Gβγ modulation. Even though both isoforms were able to physically interact with Gβγ, only the α1 GlyR was functionally modulated by Gβγ and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in α2 GlyRs was enough to generate GlyRs modulated by Gβγ and low ethanol concentrations. Interestingly, although we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open-activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two ligand-gated ion receptor members based on selective Gβγ modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs. 相似文献
43.
Mervyn Beukes Yolandy Lemmer Madrey Deysel Juma’a R. Al Dulayymi Mark S. Baird Gani Koza Maximiliano M. Iglesias Richard R. Rowles Cornelia Theunissen Johan Grooten Gianna Toschi Vanessa V. Roberts Lynne Pilcher Sandra Van Wyngaardt Nsovo Mathebula Mohammed Balogun Anton C. Stoltz Jan A. Verschoor 《Chemistry and physics of lipids》2010,163(8):800-808
Cell wall mycolic acids (MA) from Mycobacterium tuberculosis (M.tb) are CD1b presented antigens that can be used to detect antibodies as surrogate markers of active TB, even in HIV coinfected patients. The use of the complex mixtures of natural MA is complicated by an apparent antibody cross-reactivity with cholesterol. Here firstly we report three recombinant monoclonal scFv antibody fragments in the chicken germ-line antibody repertoire, which demonstrate the possibilities for cross-reactivity: the first recognized both cholesterol and mycolic acids, the second mycolic acids but not cholesterol, and the third cholesterol but not mycolic acids. Secondly, MA structure is experimentally interrogated to try to understand the cross-reactivity. Unique synthetic mycolic acids representative of the three main functional classes show varying antigenicity against human TB patient sera, depending on the functional groups present and on their stereochemistry. Oxygenated (methoxy- and keto-) mycolic acid was found to be more antigenic than alpha-mycolic acids. Synthetic methoxy-mycolic acids were the most antigenic, one containing a trans-cyclopropane apparently being somewhat more antigenic than the natural mixture. Trans-cyclopropane-containing keto- and hydroxy-mycolic acids were also found to be the most antigenic among each of these classes. However, none of the individual synthetic mycolic acids significantly and reproducibly distinguished the pooled serum of TB positive patients from that of TB negative patients better than the natural mixture of MA. This argues against the potential to improve the specificity of serodiagnosis of TB with a defined single synthetic mycolic acid antigen from this set, although sensitivity may be facilitated by using a synthetic methoxy-mycolic acid. 相似文献
44.
Santander VS Bisig CG Purro SA Casale CH Arce CA Barra HS 《Molecular and cellular biochemistry》2006,291(1-2):167-174
In cells of neural and non-neural origin, tubulin forms a complex with plasma membrane Na+,K+-ATPase, resulting in inhibition of the enzyme activity. When cells are treated with 1 mM L-glutamate, the complex is dissociated and enzyme activity is restored. Now, we found that in CAD cells, ATPase is not activated by L-glutamate and tubulin/ATPase complex is not present in membranes. By investigating the causes for this characteristic, we found that tubulin must be acetylated in order to associate with ATPase and to inhibit its catalytic activity. In CAD cells, the acetylated tubulin isotype is absent. Treatment of CAD cells with deacetylase inhibitors (trichostatin A or tubacin) caused appearance of acetylated tubulin, formation of tubulin/ATPase complex, and reduction of membrane ATPase activity. In these treated cells, addition of 1 mM L-glutamate dissociated the complex and restored the enzyme activity. Cytosolic tubulin from trichostatin A-treated but not from non-treated cells inhibited ATPase activity. These findings indicate that the acetylated isotype of tubulin is required for interaction with membrane Na+,K+-ATPase and consequent inhibition of enzyme activity. 相似文献
45.
Ortega A Romero M Izquierdo A Troyano N Arce Y Ardura JA Arenas MI Bover J Esbrit P Bosch RJ 《Journal of cellular physiology》2012,227(5):1980-1987
Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1. 相似文献
46.
The role of selective breeding and biosecurity in the prevention of disease in penaeid shrimp aquaculture 总被引:3,自引:0,他引:3
About 3.5 million metric tons of farmed shrimp were produced globally in 2009 with an estimated value greater than USD$14.6 billion. Despite the economic importance of farmed shrimp, the global shrimp farming industry continues to be plagued by disease. There are a number of strategies a shrimp farmer can employ to mitigate crop loss from disease, including the use of Specific Pathogen Free (SPF), selectively bred shrimp and the adoption of on-farm biosecurity practices. Selective breeding for disease resistance began in the mid 1990s in response to outbreaks of Taura syndrome, caused by Taura syndrome virus (TSV), which devastated populations of farmed shrimp (Litopenaeus vannamei) throughout the Americas. Breeding programs designed to enhance TSV survival have generated valuable information about the quantitative genetics of disease resistance in shrimp and have produced shrimp families which exhibit high survival after TSV exposure. The commercial availability of these selected shrimp has benefitted the shrimp farming industry and TSV is no longer considered a major threat in many shrimp farming regions. Although selective breeding has been valuable in combating TSV, this approach has not been effective for other viral pathogens and selective breeding may not be the most effective strategy for the long-term viability of the industry. Cost-effective, on-farm biosecurity protocols can be more practical and less expensive than breeding programs designed to enhance disease resistance. Of particular importance is the use of SPF shrimp stocked in biosecure environments where physical barriers are in place to mitigate the introduction and spread of virulent pathogens. 相似文献
47.
Rosa Gómez M. Isabel Arce J. Javier Sánchez M. del Mar Sánchez-Montoya 《Hydrobiologia》2012,679(1):43-59
Mediterranean climates predispose aquatic systems to both flood and drought periods, therefore, stream sediments may be exposed
to desiccation periods. Changes in oxygen concentrations and sediment water content influence the biotic processes implicated
in nitrogen dynamics. The objectives of this study were to identify (1) the changes of inorganic nitrogen in stream sediments
during the transition from wet to dry conditions, and (2) the underlying processes in N dynamics and its regulation. Extractable
sediment NO3
−-N and NH4
+-N, organic matter and extractable organic carbon content were assessed during natural desiccation in microcosms with sediments
from an intermittent Mediterranean stream. In agreement with our initial hypothesis, our results showed how the NO3
−-N content of the sediment was enhanced during the first 10 days of sediment drying, whereas NH4
+-N was lost by 14 days post-drying. During the first 10 days, sediment desiccation seemed to stimulate the net N-mineralization
and net nitrification from sediments. Afterwards, the extractable NO3
−-N concentration sharply dropped, which may be attributed to lower ammonium-oxidation rates as ammonium and organic matter
are depleted, and to an increase in NO3
−-N consumption by microbial populations. Denitrification was inhibited, with a significant decrease as % water-filled pore
space lowered. We hypothesize that the sediment inorganic N content enhanced during sediment desiccation could be released
as part of the N pulse observed after sediment rewetting. However, the stream N availability after rewetting dried sediments
would differ depending on desiccation period duration. 相似文献
48.
Connelly L Jang H Arce FT Ramachandran S Kagan BL Nussinov R Lal R 《Biochemistry》2012,51(14):3031-3038
Alzheimer's disease (AD) is a misfolded protein disease characterized by the accumulation of β-amyloid (Aβ) peptide as senile plaques, progressive neurodegeneration, and memory loss. Recent evidence suggests that AD pathology is linked to the destabilization of cellular ionic homeostasis mediated by toxic pores made of Aβ peptides. Understanding the exact nature by which these pores conduct electrical and molecular signals could aid in identifying potential therapeutic targets for the prevention and treatment of AD. Here using atomic force microscopy (AFM) and molecular dynamics (MD) simulations, we compared the imaged pore structures with models to predict channel conformations as a function of amino acid sequence. Site-specific amino acid (AA) substitutions in the wild-type Aβ(1-42) peptide yield information regarding the location and significance of individual AA residues to its characteristic structure-activity relationship. We selected two AAs that our MD simulation predicted to inhibit or permit pore conductance. The substitution of Phe19 with Pro has previously been shown to eliminate conductance in the planar lipid bilayer system. Our MD simulations predict a channel-like shape with a collapsed pore, which is supported by the AFM channel images. We suggest that proline, a known β-sheet breaker, creates a kink in the center of the pore and prevents conductance via blockage. This residue may be a viable target for drug development studies aiming to inhibit Aβ from inducing ionic destabilization toxicity. The substitution of Phe20 with Cys exhibits pore structures indistinguishable from the wild type in AFM images. MD simulations predict site 20 to face the solvated pore. Overall, the mutations support the previously predicted β-sheet-based channel structure. 相似文献
49.
Silvia Noemí López Fresy Arce Rojas Vladimir Villalba Velásquez Cynthia Cagnotti 《Biocontrol Science and Technology》2012,22(10):1107-1117
The predator Tupiocoris cucurbitaceus is frequently found attacking Trialeurodes vaporariorum in greenhouses without pesticide applications in Argentina. The objective of these studies was to evaluate some biological characteristics of this species fed on three types of diet (whitefly nymphs, Sitotroga cerealella eggs and a mix of both) and on two host plants (tomato and tobacco), under controlled experimental conditions. Preimaginal developmental time for female and male bugs was shorter in the presence of whiteflies than with only moth eggs. Females lived longer when they ate only whitefly nymphs compared to a mixed diet or only moth eggs. The amount of adult descendants was greater when bugs could eat whiteflies, regardless of the presence of S. cerealella. Embryonic development time, male longevity and sex proportion were not affected by the diet or the host plant. Prey consumption was evaluated for three T. cucurbitaceus life history stages (fourth/fifth instar nymphs, female and male adults) on two types of prey (whitefly nymphs and S. cerealella eggs). On tomato, females were more voracious than males and nymphs. On tobacco, adults and nymphs consumed more S. cerealella than T.vaporariorum nymphs, but again, bug females preyed more than males and nymphs. Results demonstrate that T. cucurbitaceus can survive, develop and reproduce normally using both T. vaporariorum and S. cerealella eggs as prey on tobacco or tomato plants. This information can be useful for managing this predator against T. vaporariorum through conservative or augmentative biological control strategies. 相似文献
50.