全文获取类型
收费全文 | 401篇 |
免费 | 16篇 |
专业分类
417篇 |
出版年
2023年 | 2篇 |
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 2篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 14篇 |
2015年 | 21篇 |
2014年 | 26篇 |
2013年 | 22篇 |
2012年 | 37篇 |
2011年 | 42篇 |
2010年 | 27篇 |
2009年 | 11篇 |
2008年 | 35篇 |
2007年 | 25篇 |
2006年 | 27篇 |
2005年 | 16篇 |
2004年 | 21篇 |
2003年 | 20篇 |
2002年 | 14篇 |
2001年 | 4篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1985年 | 2篇 |
排序方式: 共有417条查询结果,搜索用时 15 毫秒
101.
Oxidative DNA damage: assessment of the role in carcinogenesis,atherosclerosis, and acquired immunodeficiency syndrome 总被引:1,自引:0,他引:1
Olinski R Gackowski D Foksinski M Rozalski R Roszkowski K Jaruga P 《Free radical biology & medicine》2002,33(2):192-200
Free radical attack upon DNA generates a multiplicity of DNA damage, including modified bases. Some of these modifications have considerable potential to damage the integrity of the genome. This article reviews recent data that suggest the involvement of oxidative DNA damage in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome (AIDS). There is evidence that oxidative DNA damage may play a causative role in atherosclerosis. Oxidative DNA damage may lead to apoptotic cell death of patients infected with human immunodeficiency virus (HIV) and may influence the progression of AIDS. While many details regarding the role of reactive oxygen species-induced DNA damage in the etiology of complex multifactorial diseases like cancer are yet to be discovered, evidence suggests that oxidants act at several stages in the malignant transformation of cells. However, the quantitative relationship between the measured DNA damage and the development of cancer is still lacking. 相似文献
102.
The high-throughput - next generation sequencing (HT-NGS) technologies are currently the hottest topic in the field of human
and animals genomics researches, which can produce over 100 times more data compared to the most sophisticated capillary sequencers
based on the Sanger method. With the ongoing developments of high throughput sequencing machines and advancement of modern
bioinformatics tools at unprecedented pace, the target goal of sequencing individual genomes of living organism at a cost
of $1,000 each is seemed to be realistically feasible in the near future. In the relatively short time frame since 2005, the
HT-NGS technologies are revolutionizing the human and animal genome researches by analysis of chromatin immunoprecipitation
coupled to DNA microarray (ChIP-chip) or sequencing (ChIP-seq), RNA sequencing (RNA-seq), whole genome genotyping, genome
wide structural variation, de novo assembling and re-assembling of genome, mutation detection and carrier screening, detection
of inherited disorders and complex human diseases, DNA library preparation, paired ends and genomic captures, sequencing of
mitochondrial genome and personal genomics. In this review, we addressed the important features of HT-NGS like, first generation
DNA sequencers, birth of HT-NGS, second generation HT-NGS platforms, third generation HT-NGS platforms: including single molecule
Heliscope™, SMRT™ and RNAP sequencers, Nanopore, Archon Genomics X PRIZE foundation, comparison of second and third HT-NGS
platforms, applications, advances and future perspectives of sequencing technologies on human and animal genome research. 相似文献
103.
Liwarska-Bizukojc E Olejnik D Biernacki R Ledakowicz S 《Bioprocess and biosystems engineering》2011,34(6):659-670
In this study, the results of the calibration of the complex activated sludge model implemented in BioWin software for the
full-scale wastewater treatment plant are presented. Within the calibration of the model, sensitivity analysis of its parameters
and the fractions of carbonaceous substrate were performed. In the steady-state and dynamic calibrations, a successful agreement
between the measured and simulated values of the output variables was achieved. Sensitivity analysis revealed that upon the
calculations of normalized sensitivity coefficient (S
i,j
) 17 (steady-state) or 19 (dynamic conditions) kinetic and stoichiometric parameters are sensitive. Most of them are associated
with growth and decay of ordinary heterotrophic organisms and phosphorus accumulating organisms. The rankings of ten most
sensitive parameters established on the basis of the calculations of the mean square sensitivity measure (δ
j
msqr) indicate that irrespective of the fact, whether the steady-state or dynamic calibration was performed, there is an agreement
in the sensitivity of parameters. 相似文献
104.
The evolutionary implications of recombination in HIV remain not fully understood. A plausible effect could be an enhancement of immune escape from cytotoxic T lymphocytes (CTLs). In order to test this hypothesis, we constructed a population dynamic model of immune escape in HIV and examined the viral-immune dynamics with and without recombination. Our model shows that recombination (i) increases the genetic diversity of the viral population, (ii) accelerates the emergence of escape mutations with and without compensatory mutations, and (iii) accelerates the acquisition of immune escape mutations in the early stage of viral infection. We see a particularly strong impact of recombination in systems with broad, non-immunodominant CTL responses. Overall, our study argues for the importance of recombination in HIV in allowing the virus to adapt to changing selective pressures as imposed by the immune system and shows that the effect of recombination depends on the immunodominance pattern of effector T cell responses. 相似文献
105.
Pareek CS Smoczynski R Pierzchala M Czarnik U Tretyn A 《Briefings in functional genomics》2011,10(3):165-171
In past 5 years, the promise that came with genome sequencing has revolutionized the functional genomics research field at unprecedented manner. It would soon know what all known genes do, particularly genes involved in genetic improvement of animal health and increase food animal production. With the availability of full bovine genomic sequence, yet we still have a lot of daunting tasks on 'genotype-to-phenotype problem' particularly about the phenotypic variations and trying to predict what genes are likely to be involved, and improved integrated interactive database. This article outlined and discussed about the current status of bovine functional genomics, recent development in bovine genome databases particularly in annotation of bovine genome, bovine quantitative trait loci database and its potential impact to unveil the from genotype-to-phenotype problem. 相似文献
106.
Thomas C. Cassey David R. Evens Rafal Bogacz James A. R. Marshall Casimir J. H. Ludwig 《PloS one》2013,8(11)
In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy. 相似文献
107.
Bronislaw A. Zachara Jolanta Gromadzinska Jadwiga Palus Zbigniew Zbrog Rafal Swiech Ewa Twardowska Wojciech Wasowicz 《Biological trace element research》2011,142(3):274-283
Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis
(HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation
to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD
patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients
were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration
in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative
bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly
lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients
at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients
on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA. 相似文献
108.
Kapoor N Lee W Clark E Bartoszewski R McNicholas CM Latham CB Bebok Z Parpura V Fuller CM Palmer CA Benos DJ 《American journal of physiology. Cell physiology》2011,300(6):C1246-C1259
Glioblastoma multiforme (GBM) is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the epithelial sodium channel (ENaC)/degenerin (Deg) family and are associated with a basally active amiloride-sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of ENaC and acid-sensing ion channel (ASIC) subunits. To test the hypothesis that ASIC1 interacts with αENaC and γENaC at the cellular level, we have used total internal reflection fluorescence microscopy (TIRFM) in live rat astrocytes transiently cotransfected with cDNAs for ASIC1-DsRed plus αENaC-yellow fluorescent protein (YFP) or ASIC1-DsRed plus γENaC-YFP. TIRFM images show colocalization of ASIC1 with both αENaC and γENaC. Furthermore, using TIRFM in stably transfected D54-MG cells, we also found that ASIC1 and αENaC both localize to a submembrane region following exposure to pH 6.0, similar to the acidic conditions found in the core of a glioblastoma lesion. Using high-resolution clear native gel electrophoresis, we found that ASIC1 forms a complex with ENaC subunits which migrates at ≈480 kDa in D54-MG glioma cells. These data suggest that different ENaC/Deg subunits interact and could combine to form a hybrid channel that likely underlies the amiloride-sensitive current seen in human glioma cells. 相似文献
109.
Foksinski M Rozalski R Guz J Ruszkowska B Sztukowska P Piwowarski M Klungland A Olinski R 《Free radical biology & medicine》2004,37(9):1449-1454
Using recently developed methodology, which includes HPLC prepurification followed by GC/MS with isotope dilution, we analyzed urinary excretion of possible repair products of oxidative DNA damage-8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 5-(hydroxymethyl)uracil (5-HMUra)-in mammalian species that substantially differ in metabolic rate and longevity, namely, mice, rats, rabbits, dogs, pigs, and humans. We found highly significant, positive correlations between specific metabolic rates of the animals studied and their excretion rates for all the modifications analyzed with respective r values for the lesions of (8-oxoGua) r = .891, p < .01; (8-oxodG) r = .998, p < .001; and (5-HMUra) r = .949, p < .005. However, only 8-oxoGua significantly correlates negatively with maximum life span (MLSP) (r = -.928, p < .01). Despite substantial differences in MLSP between humans and pigs (120 and 27 years, respectively), the rates of excretion of all measured modifications were very similar. The urinary levels of all measured modifications found in our study for mouse and humans account respectively for about 34,000 and 2800 repaired events per average cell, per 24 h. It is therefore possible that the high metabolic rate in mice (or other short-lived animals) may be responsible for severe everyday oxidative DNA insults that may be accumulated faster than in long-lived species. 相似文献
110.
A new regioselective method of di-gem-thio-substituted PNP-crown derivatives synthesis is presented. The geminalmercaptoethanolanetricyclophosphaza-PNP-lariat ether structure has been determined by X-ray crystallography and characterised by ab initio calculations. The 16-membered PNP-crown ether ring exists in unique conformation: ac−ap ac−sc+sc+ap sc+ap ap sc−ap sc−sc−ac+ap ac+. All the ether oxygen atoms are directed into the interior of the ring. All endocyclic P-N bond lengths are equal within experimental error with the mean value 1.578(2) Å. The P-S bond properties have been characterised in terms of natural bond orbital (NBO) analysis, and its interactions with other NBO have been described. The spirocyclisation mechanism at cyclophosphazene phosphorus atom has been proposed. 相似文献