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101.

Background

Coral reefs face increasing pressures particularly when on the edge of their distributions. The Houtman Abrolhos Islands (Abrolhos) are the southernmost coral reef system in the Indian Ocean, and one of the highest latitude reefs in the world. These reefs have a unique mix of tropical and temperate marine fauna and flora and support 184 species of coral, dominated by Acropora species. A significant La Niña event during 2011 produced anomalous conditions of increased temperature along the whole Western Australian coastline, producing the first-recorded widespread bleaching of corals at the Abrolhos.

Methodology/ Principal Findings

We examined long term trends in the marine climate at the Abrolhos using historical sea surface temperature data (HadISST data set) from 1900–2011. In addition in situ water temperature data for the Abrolhos (from data loggers installed in 2008, across four island groups) were used to determine temperature exposure profiles. Coupled with the results of coral cover surveys conducted annually since 2007; we calculated bleaching thresholds for monitoring sites across the four Abrolhos groups.

Conclusions/ Significance

In situ temperature data revealed maximum daily water temperatures reached 29.54°C in March 2011 which is 4.2°C above mean maximum daily temperatures (2008–2010). The level of bleaching varied across sites with an average of ∼12% of corals bleached. Mortality was high, with a mean ∼50% following the 2011 bleaching event. Prior to 2011, summer temperatures reached a mean (across all monitoring sites) of 25.1°C for 2.5 days. However, in 2011 temperatures reached a mean of 28.1°C for 3.3 days. Longer term trends (1900–2011) showed mean annual sea surface temperatures increase by 0.01°C per annum. Long-term temperature data along with short-term peaks in 2011, outline the potential for corals to be exposed to more frequent bleaching risk with consequences for this high latitude coral reef system at the edge of its distribution.  相似文献   
102.
Activation of the human carbonic anhydrase (CA, EC 4.2.1.1) isozymes I, II (cytosolic) and IX (transmembrane, tumor-associated isoform) with a series of arylsulfonylhydrazido-l-histidines incorporating 4-substituted-phenyl, pentafluorophenyl- and β-naphthyl moieties was investigated. The compounds showed a weak hCA I activation profile, but were more efficient as hCA II and IX activators. The 4-iodophenyl-substituted derivative behaved as a strong and isozyme selective hCA II activator, with an activation constant of 0.21 μM. This is the first isoform-selective, potent CA activator reported to date.  相似文献   
103.
  • Heavy metals are characterised by a relatively high density and cause genotoxic, cytotoxic and mutagenic effects on plants, animals and humans. Lead (Pb) is one of the heavy metals that causes toxicity to plants and animals.
  • This experiment was conducted using a hydroponic technique to study the effects of Pb(NO3)2 on physiological, biochemical and ultrastructural characteristics in Leucaena leucocephala seedlings. Plants were grown in a growth chamber for 21 days in Hoagland’s solution supplemented with 0 (control), 25, 50, 100, 300, 500 and 700 µm Pb(NO3)2.
  • Shoot heights as well as root lengths decreased significantly in Pb‐treated plants with 300, 500 and 700 µm . In Pb‐treated plants with high Pb concentrations, photosynthesis rate (PN), stomatal conductance (gs) and transpiration rate (E) decreased. Total protein and carbohydrate content in Pb‐treated plants with 300, 500 and 700 µm increased significantly in leaves. Moreover, in Pb‐treated plants with 300, 500 and 700 µm Pb(NO3)2, mesophyll cells had enlarged chloroplasts with disrupted thylakoid membranes associated with large starch grains. In contrast, Pb treatments with 25, 50 µm and 100 µm were not toxic to the plants. Thick sections of roots of Pb‐treated plants with 300, 500 and 700 µm Pb showed distinct changes in structure of epidermal and cortical cells. Moreover, thin sections of roots of Pb‐treated plants with 300, 500 and 700 µm Pb had thickened walls of xylem cells.
  • These results will shed more light in understanding the effects of heavy metal stress on plants.
  相似文献   
104.
Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.  相似文献   
105.
Recently, the use of the Bayesian network as an alternative to existing tools for similarity-based virtual screening has received noticeable attention from researchers in the chemoinformatics field. The main aim of the Bayesian network model is to improve the retrieval effectiveness of similarity-based virtual screening. To this end, different models of the Bayesian network have been developed. In our previous works, the retrieval performance of the Bayesian network was observed to improve significantly when multiple reference structures or fragment weightings were used. In this article, the authors enhance the Bayesian inference network (BIN) using the relevance feedback information. In this approach, a few high-ranking structures of unknown activity were filtered from the outputs of BIN, based on a single active reference structure, to form a set of active reference structures. This set of active reference structures was used in two distinct techniques for carrying out such BIN searching: reweighting the fragments in the reference structures and group fusion techniques. Simulated virtual screening experiments with three MDL Drug Data Report data sets showed that the proposed techniques provide simple ways of enhancing the cost-effectiveness of ligand-based virtual screening searches, especially for higher diversity data sets.  相似文献   
106.
The current available treatment for hepatitis C virus (HCV)—the causative of liver cirrhosis and development of liver cancer—is a dual therapy using modified interferon and ribavirin. While this regimen increases the sustained viral response rate up to 40–80 % in different genotypes, unfortunately, it is poorly tolerated by patients. PSI-7977, a prodrug for PSI-7409, is a Non-Structural 5b (NS5b) polymerase nucleoside inhibitor that is currently in phase III clinical trials. The activated PSI-7977 is a direct acting antiviral (DAA) drug that acts on NS5b polymerase of HCV through a coordination bond with the two Mg+2 present at the GDD active site motif. The present work utilizes a molecular modeling approach for studying the interaction between the activated PSI-7977 and the 12 amino acids constituting a 5 Å region surrounding the GDD active triad motif for HCV genotypes 1a, 2b, 3b and 4a. The analysis of the interaction parameters suggests that PSI-7977 is probably a better DAA drug for HCV genotypes 1a and 3b rather than genotypes 2b and 4a.  相似文献   
107.
108.
Gluconeogenesis, the reverse process of glycolysis, is a favorable mechanism at conditions of glucose deprivation. Pck1 is a rate‐limiting gluconeogenic enzyme, where its deficiency or mutation contributes to serious clinical situations as neonatal hypoglycemia and liver failure. A recent report confirms that Pck1 is a target for proteasomal degradation through its proline residue at the penultimate position, recognized by Gid4 E3 ligase, but with a lack of informative structural details. In this study, we delineate the localized sequence motif, degron, that specifically interact with Gid4 ligase and unravel the binding mode of Pck1 to the Gid4 ligase by using molecular docking and molecular dynamics. The peptide/protein docking HPEPDOCK web server along with molecular dynamic simulations are applied to demonstrate the binding mode and interactions of a Pck1 wild type (SPSK) and mutant (K4V) with the recently solved structure of Gid4 ligase. Results unveil a distinct binding mode of the mutated peptide compared with the wild type despite having comparable binding affinities to Gid4. Moreover, the four‐residue peptide is found insufficient for Gid4 binding, while the seven‐residue peptide suffices for binding to Gid4. The amino acids S134, K135, and N137 in the loop L1 (between β1 and β2) of the Gid4 are essential for the stabilization of the seven‐residue peptide in the binding site of the ligase. The presence of Val4 instead of Lys4 smashes the H‐bonds that are formed between Lys4 and Gid4 in the wild type peptide, making the peptide prone to bind with the other side of the binding pocket (L4 loop of Gid4). The dynamics of Gid4 L3 loop is affected dramatically once K4V mutant Pck1 peptide is introduced. This opens the door to explore the mutation effects on the binding mode and smooth the path to target protein degradation by design competitive and non‐competitive inhibitors.  相似文献   
109.
In indigenous populations, age can be estimated based on family structure and physical examination. However, the accuracy of such methods is questionable. The aim of this cross-sectional study was to evaluate occlusal tooth wear related to estimated age in the remote indigenous populations of the Xingu River, Amazon. Two hundred and twenty three semi-isolated indigenous subjects with permanent dentition from the Arara (n = 117), Xicrin-Kayapó (n = 60) and Assurini (n = 46) villages were examined. The control group consisted of 40 non-indigenous individuals living in an urban area in the Amazon basin (Belem). A modified tooth wear index was applied and then associated with chronological age by linear regression analysis. A strong association was found between tooth wear and chronological age in the indigenous populations (p <0.001). Tooth wear measurements were able to explain 86% of the variation in the ages of the Arara sample, 70% of the Xicrin-Kaiapó sample and 65% of the Assurini sample. In the urban control sample, only 12% of ages could be determined by tooth wear. These findings suggest that tooth wear is a poor estimator of chronological age in the urban population; however, it has a strong association with age for the more remote indigenous populations. Consequently, these findings suggest that a simple tooth wear evaluation method, as described and applied in this study, can be used to provide a straightforward and efficient means to assist in age determination of newly contacted indigenous groups.  相似文献   
110.
This study examined the psychometric properties of an Argentine Version of the Morningness Composite (CS) and the Early/Late Preference (PS) Scales. During summer (long photoperiod in Argentina), 304 subjects (69.1% women; mean age=33.64 yrs, SD=14 yrs) completed the scales for the first time. In winter (short photoperiod), 100 of the same individuals (71% women; mean age=37.17 yrs, SD=14.63 yrs) were retested. The total scores ranged within the values reported by previous studies and were independent of gender. Older subjects showed higher morningness scores. The internal consistencies were good (CS=0.86, PS=0.82). Item 7 from the CS and items 7 and 9 from the PS showed low item‐scale correlation. Factor analysis produced a three‐factor solution for both scales. However, the inconsistency of the evening items suggests that the single‐solution may be more acceptable. Test‐retest correlations were satisfactory (CS=0.88, PS=0.78), but the two‐related‐sample test revealed significant differences between test and retest scores, suggesting relative temporal stabilities. Both scales presented similar and acceptable psychometric properties and good correlation, indicating construct validity.  相似文献   
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