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311.
Staphylococcus aureus has been recognized as an important human pathogen for more than 100 years. DNA ligase is the main protein responsible for the replication of S. aureus. DNA ligase was selected as successive target to control the replication mechanism. The antibacterial activity of polysaccharide is known. Therefore, it is of interest to study the activity of Polysaccharide analogues against DNA ligase in S. aureus using molecular docking analysis. We report ten analogues using scoring parameters with best two analogues as potential drug candidate for the combat of S. aureus infection. 相似文献
312.
Selvan Nehru John Abraham Anitha Priya Sekar Hariharan Rajadurai Vijay Solomon Selvakumar Veeralakshmi 《Journal of biomolecular structure & dynamics》2020,38(7):2057-2067
AbstractFor efficient designing of metallodrugs, it is imperative to analyse the binding affinity of those drugs with drug-carrying serum albumins to comprehend their structure–activity correlation for biomedical applications. Here, cobalt(II) and cobalt(III) complexes comprising three phendione ligands, [Co(phendione)3]Cl2 (1) and [Co(phendione)3]Cl3 (2), where, phendione = 1,10-phenanthroline-5,6-dione, has been chosen to contrast the impact of their hydrophobicity and ionicity on binding with bovine serum albumin (BSA) through spectrophotometric titrations. The attained hydrophobicity values using octanol/water partition coefficient method manifested that complex 1 is more hydrophobic than complex 2, which could be attributed to lesser charge on its coordination sphere. The interaction of complexes 1 and 2 with BSA using steady state fluorescence studies revealed that these complexes quench the intrinsic fluorescence of BSA through static mechanism, and the extent of quenching and binding parameters are higher for complex 2. Further thermodynamics of BSA-binding studies revealed that complexes 1 and 2 interact with BSA through hydrophobic and hydrogen bonding/van der Waals interactions, respectively. Further, UV–visible absorption, circular dichroism and synchronous fluorescence studies confirmed the occurrence of conformational and microenvironmental changes in BSA upon binding with complexes 1 and 2. Molecular docking studies have also shown that complex 2 has a higher binding affinity towards BSA as compared to complex 1. This sort of modification of ionicity and hydrophobicity of metal complexes for getting desirable binding mode/strength with drug transporting serum albumins will be a promising pathway for designing active and new kind of metallodrugs for various biomedical applications.Communicated by Ramaswamy H. Sarma 相似文献
313.
Kumar Somyajit Sneha Saxena Sharath Babu Anup Mishra Ganesh Nagaraju 《Nucleic acids research》2015,43(20):9835-9855
Mammalian RAD51 paralogs are implicated in the repair of collapsed replication forks by homologous recombination. However, their physiological roles in replication fork maintenance prior to fork collapse remain obscure. Here, we report on the role of RAD51 paralogs in short-term replicative stress devoid of DSBs. We show that RAD51 paralogs localize to nascent DNA and common fragile sites upon replication fork stalling. Strikingly, RAD51 paralogs deficient cells exhibit elevated levels of 53BP1 nuclear bodies and increased DSB formation, the latter being attributed to extensive degradation of nascent DNA at stalled forks. RAD51C and XRCC3 promote the restart of stalled replication in an ATP hydrolysis dependent manner by disengaging RAD51 and other RAD51 paralogs from the halted forks. Notably, we find that Fanconi anemia (FA)-like disorder and breast and ovarian cancer patient derived mutations of RAD51C fails to protect replication fork, exhibit under-replicated genomic regions and elevated micro-nucleation. Taken together, RAD51 paralogs prevent degradation of stalled forks and promote the restart of halted replication to avoid replication fork collapse, thereby maintaining genomic integrity and suppressing tumorigenesis. 相似文献
314.
MS Nandhu Jes Paul Korah P Kuruvilla Anitha Malat Chinthu Romeo CS Paulose 《Journal of biomedical science》2011,18(1):5
Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine
depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia
is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested
to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric
acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine
induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed
a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B,
mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats
compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed
a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out
to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal
of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's
disease is of prominence. 相似文献
315.
316.
V. Thirunavukkarasu A. T. Anitha Nandhini C. V. Anuradha 《Experimental diabetes research》2004,5(4):237-244
Nonenzymatic glycation of proteins, leading to chemical
modification and cross-linking are of importance in the
pathology of diabetic complications.We studied the effect of
α-lipoic acid (LA) on the content and characteristics of the
protein collagen from skin of high-fructose fed rats. The
rats were divided into 4 groups of 6 each. Two groups of
rats were fed with a high fructose diet (60 g/100 g diet) and
administered either LA (35 mg/kg b.w., i.p) (FRU+LA) or
0.2 ml vehicle (saline) (FRU) for 45 days. The other 2 groups
were fed with control diet containing starch (60 g/100 g
diet) and administered either saline (CON) or lipoic acid
(CON+LA). The rats were maintained for 45 days and then
sacrificed. Plasma glucose, insulin, fructosamine, protein
glycation, and blood glycated hemoglobin (HbA1C) were
measured. Collagen was isolated from skin and the physicochemical
properties of collagen were studied. Fructose administration
caused accumulation of collagen in skin. Extensive
cross-linking was evidenced by enhanced glycation
and AGE-linked fluorescence. Increased peroxidation and
changes in physicochemical properties such as shrinkage
temperature, aldehyde content, solubililty pattern, susceptibility
to denaturing agents were observed in fructose-fed
rats. SDS gel pattern of collagen from these rats showed
elevated β component of type I collagen. These changes
were alleviated by the simultaneous administration of LA.
Administration of LA to fructose-fed rats had a positive
influence on both quantitative and qualitative properties of collagen. The results suggest a mechanism for the ability
of LA to delay diabetic complications. 相似文献
317.
Background Sorghum, the C4 dry-land cereal, important for food, fodder, feed and fuel, is a model crop for abiotic stress tolerance with smaller genome size, genetic diversity, and bio-energy traits. The heat shock proteins/chaperonin 60s (HSP60/Cpn60s) assist the plastid proteins, and participate in the folding and aggregation of proteins. However, the functions of HSP60s in abiotic stress tolerance in Sorghum remain unclear.MethodsGenome-wide screening and in silico characterization of SbHSP60s were carried out along with tissue and stress-specific expression analysis.ResultsA total of 36 HSP60 genes were identified in Sorghum bicolor. They were subdivided into 2 groups, the HSP60 and HSP10 co-chaperonins encoded by 30 and 6 genes, respectively. The genes are distributed on all the chromosomes, chromosome 1 being the hot spot with 9 genes. All the HSP60s were found hydrophilic and highly unstable. The HSP60 genes showed a large number of introns, the majority of them with more than 10. Among the 12 paralogs, only 1 was tandem and the remaining 11 segmental, indicating their role in the expansion of SbHSP60s. Majority of the SbHSP60 genes expressed uniformly in leaf while a moderate expression was observed in the root tissues, with the highest expression displayed by SbHSP60-1. From expression analysis, SbHSP60-3 for drought, SbHSP60-9 for salt, SbHSP60-9 and 24 for heat and SbHSP60-3, 9 and SbHSP10-2 have been found implicated for cold stress tolerance and appeared as the key regulatory genes.ConclusionThis work paves the way for the utilization of chaperonin family genes for achieving abiotic stress tolerance in plants. 相似文献
318.
A regiospecific and stereoselective total synthesis of the trisnorsesquiternene (±)-albene, via a prochiral precursor is described. The ortho ester Claisen rearrangement of the allyl alcohol, obtained in two regiospecific reactions from a Diels-Alder adduct, followed by hydrolysis of the resultant ester furnished an ene acid in a highly stereoselective manner. Anhydrous copper sulphate catalysed intramolecular cyclopropanation reaction of the diazo ketone derived from the ene acid, generated a cyclopropyl ketone. The regiospecific reductive cleavage of this cyclopropyl ketone resulted in a prochiral ketone. Finally, Shapiro reaction on the tosylhydrazone, derived from the latter ketone, furnished (±)-albene. 相似文献