全文获取类型
收费全文 | 1043篇 |
免费 | 51篇 |
专业分类
1094篇 |
出版年
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 13篇 |
2018年 | 21篇 |
2017年 | 16篇 |
2016年 | 33篇 |
2015年 | 34篇 |
2014年 | 50篇 |
2013年 | 61篇 |
2012年 | 74篇 |
2011年 | 75篇 |
2010年 | 46篇 |
2009年 | 34篇 |
2008年 | 61篇 |
2007年 | 61篇 |
2006年 | 60篇 |
2005年 | 52篇 |
2004年 | 50篇 |
2003年 | 54篇 |
2002年 | 64篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 14篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 8篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 10篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1982年 | 7篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1975年 | 7篇 |
1973年 | 7篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1956年 | 2篇 |
1953年 | 5篇 |
排序方式: 共有1094条查询结果,搜索用时 15 毫秒
81.
Wioletta Wujcicka Edyta Paradowska Miros?awa Studzińska Zuzanna Gaj Jan Wilczyński Zbigniew Le?nikowski Dorota Nowakowska 《PloS one》2015,10(4)
Background
Some single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital cytomegaly, based on available samples.Methods
Reported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital cytomegaly development was estimated, using a logistic regression model.Results
Hardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic cytomegaly (P≤0.0001).Conclusions
TLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital cytomegaly development. 相似文献82.
Magdalena Wiecek Marcin Maciejczyk Jadwiga Szymura Zbigniew Szygula Malgorzata Kantorowicz 《PloS one》2015,10(11)
Purpose
The aim of this study was to compare changes in total oxidative status (TOS), total antioxidative capacity (TAC) and the concentration of VitA, VitE, VitC, uric acid (UA), reduced (GSH) and oxidized glutathione (GSSG) in blood within 24 hours following anaerobic exercise (AnEx) among men and women.Methods
10 women and 10 men performed a 20-second bicycle sprint (AnEx). Concentrations of oxidative stress indicators were measured before AnEx and 3, 15 and 30 minutes and 1 hour afterwards. UA, GSH and GSSH were also measured 24 hours after AnEx. Lactate and H+ concentrations were measured before and 3 minutes after AnEx.Results
The increase in lactate and H+ concentrations following AnEx was similar in both sexes. Changes in the concentrations of all oxidative stress indicators were significant and did not differ between men and women. In both sexes, TOS, TAC, TOS/TAC and VitA and VitE concentrations were the highest 3 minutes, VitC concentration was the highest 30 minutes, and UA concentration was the highest 1 hour after AnEx. GSH concentration was significantly lower than the initial concentration from 15 minutes to 24 hour after AnEx. GSSG concentration was significantly higher, while the GSH/GSSG ratio was significantly lower than the initial values 1 hour and 24 hour after AnEx.Conclusions
With similar changes in lactate and H+ concentrations, AnEx induces the same changes in TAC, TOS, TOS/TAC and non-enzymatic antioxidants of low molecular weight in men and women. Oxidative stress lasted at least 24 hours after AnEx. 相似文献83.
Magdalena Paczkowska Miko?aj Mizera Hanna Piotrowska Daria Szymanowska-Powa?owska Kornelia Lewandowska Joanna Goscianska Robert Pietrzak Waldemar Bednarski Zbigniew Majka Judyta Cielecka-Piontek 《PloS one》2015,10(3)
This study aimed to obtain and characterize an RU-β-CD complex in the context of investigating the possibility of changes in the solubility, stability, antioxidative and microbiological activity as well as permeability of complexated rutin as against its free form. The formation of the RU-β-CD complex via a co-grinding technique was confirmed by using DSC, SEM, FT-IR and Raman spectroscopy, and its geometry was assessed through molecular modeling. It was found that the stability and solubility of the so-obtained complex were greater compared to the free form; however, a slight decrease was observed inits antibacterial potency. An examination of changes in the EPR spectra of thecomplex excluded any reducing effect of complexation on the antioxidative activity of rutin. Considering the prospect of preformulation studies involving RU-β-CD complexes, of significance is also the observed possibility of prolongedly releasing rutin from the complex at a constant level over along period of 20 h, and the fact that twice as much complexated rutin was able topermeate compared to its free form. 相似文献
84.
85.
Piotr Stefanowicz Monika Kijewska Katarzyna Kapczyńska Zbigniew Szewczuk 《Amino acids》2010,38(3):881-889
Two procedures of glycated peptides’ synthesis have been developed. The first method involves reductive alkylation of the
ε-amino groups of lysine with 2,3:4,5-di-O-isopropylidene-β-d-arabino-hexos-2-ulo-2,6-pyranose in the presence of sodium cyanoborohydride on solid support. The second one uses a new fully
protected lysine derivative, which is a building block designed for direct introduction of the glycated lysine moiety into
a peptide, according to the standard solid phase synthesis protocol. The applicability of the proposed methods for the synthesis
of peptide-derived Amadori products is discussed. The structure of the synthesized glycated peptides was confirmed by high-resolution
mass spectrometry and enzymatic hydrolysis. Circular dichroism studies, performed in water solution, revealed that the formation
of the Amadori rearrangement product in the lysine side chain does not influence significantly the conformational preferences
of the peptides studied. However, when the solvent was changed to trifluoroethanol, the glycated peptides preferred β-turn
conformation. 相似文献
86.
Zbigniew Szybiński Stanisław Walas Paweł Zagrodzki Grzegorz Sokołowski Filip Gołkowski Halina Mrowiec 《Biological trace element research》2010,138(1-3):28-41
The purpose of this work was to determine trace element levels in urine and evaluate possible associations between urinary iodine concentration (UIC), other trace elements (Cr, Cu, Fe, Mn, Na, Se, Zn), toxic elements (Cd, Pb), anthropometrical measures (body weight and height), glycemic indices (serum insulin and glucose), and several parameters related to thyroid function (thyroid stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, thyroid volume, and thyroid echogenicity) in pregnant women. One hundred sixty-nine participants were recruited. The whole study group, originating from Krakow region, comprised three subgroups belonging to three trimesters: I trimester (n?=?28), II trimester (n?=?83), and III trimester (n?=?58). Trace elements were determined using inductively coupled plasma mass/(atomic emission) spectrometry. Partial least square model was used to reveal correlation structure between parameters investigated, as well as a possible causal relationship between dependent parameters and potentially explanatory parameters. Results obtained for trace and toxic elements in urine were comparable with results of other authors, although the study group was not homogenous. We confirmed (1) low iodine excretion in pregnant women, (2) the existence of statistically significant correlation between UIC and urinary selenium, and (3) lack of correlation between latter parameter and typical indices of thyroid function. Urinary selenium correlated with other urinary trace elements, but physiological significance of this finding remains uncertain. The fact that a large number of pregnant women fail to meet dietary recommendations for iodine is the major reason for concern. 相似文献
87.
Protective action of melatonin against oxidative DNA damage: chemical inactivation versus base-excision repair 总被引:2,自引:0,他引:2
Sliwinski T Rozej W Morawiec-Bajda A Morawiec Z Reiter R Blasiak J 《Mutation research》2007,634(1-2):220-227
Melatonin is a hormone-like substance that has a variety of beneficial properties as regulator of the circadian rhythm and as anti-inflammatory and anti-cancer agent. The latter activity can be linked with the ability of melatonin to protect DNA against oxidative damage. It may exert such action either by scavenging reactive oxygen species or their primary sources, or by stimulating the repair of oxidative damage in DNA. Since such type of DNA damage is reflected in oxidative base modifications that are primarily repaired by base-excision repair (BER), we tried to investigate in the present work whether melatonin could influence this DNA-repair system. We also investigated the ability of melatonin to inactivate hydrogen peroxide, a potent source of reactive oxygen species. Melatonin at 50 microM and its direct metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine reduced DNA damage induced by hydrogen peroxide at approximately the same ratio. Melatonin stimulated the repair of DNA damage induced by hydrogen peroxide, as assessed by the alkaline comet assay. However, melatonin at 50 microM had no impact on the activity in vitro of three glycosylases playing a pivotal role in BER: Endo III, Fpg and ANPG 80. On the other hand, melatonin chemically inactivated hydrogen peroxide, reducing its potential to damage DNA. And finally, melatonin did not influence the repair of an a-basic (AP) site by cellular extracts, as was evaluated by a functional BER assay in vitro. In conclusion, melatonin can have a protective effect against oxidative DNA damage by chemical inactivation of a DNA-damaging agent as well as by stimulating DNA repair, but key factors in BER, viz. glycosylases and AP-endonucleases, do not seem to be affected by melatonin. Further study with other components of the BER machinery and studies aimed at other DNA-repair systems are needed to clarify the mechanism underlying the stimulation of DNA repair by melatonin. 相似文献
88.
Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Melquist S Craig DW Huentelman MJ Crook R Pearson JV Baker M Zismann VL Gass J Adamson J Szelinger S Corneveaux J Cannon A Coon KD Lincoln S Adler C Tuite P Calne DB Bigio EH Uitti RJ Wszolek ZK Golbe LI Caselli RJ Graff-Radford N Litvan I Farrer MJ Dickson DW Hutton M Stephan DA 《American journal of human genetics》2007,80(4):769-778
To date, only the H1 MAPT haplotype has been consistently associated with risk of developing the neurodegenerative disease progressive supranuclear palsy (PSP). We hypothesized that additional genetic loci may be involved in conferring risk of PSP that could be identified through a pooling-based genomewide association study of >500,000 SNPs. Candidate SNPs with large differences in allelic frequency were identified by ranking all SNPs by their probe-intensity difference between cohorts. The MAPT H1 haplotype was strongly detected by this methodology, as was a second major locus on chromosome 11p12-p11 that showed evidence of association at allelic (P<.001), genotypic (P<.001), and haplotypic (P<.001) levels and was narrowed to a single haplotype block containing the DNA damage-binding protein 2 (DDB2) and lysosomal acid phosphatase 2 (ACP2) genes. Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease. 相似文献
89.
Chewing lice of the species Docophorulus coarctatus were extracted from museum specimens of their host, the great grey shrike Lanius excubitor, by combing feathers from 36 freshly shot birds (shot between 1962 and 1974), and samples of ten individual lice (five female,
five male) were randomly collected for measurements from each bird. Female lice were bigger than males for all studied measurements
(P < 0.001 in all cases), although the size of both sexes obtained from individual hosts was positively correlated. The overall
size of lice (derived from a principal components analysis) was positively correlated with the overall size of the avian host,
and also with the population density of lice on the individual host. We suggest that variation in louse morphology is due
to differences in selection pressure exerted by each host and by intraspecific competition due to conspecifics. This is, to
the best of our knowledge, the first evidence that Harrison’s rule (parasites on larger host species are often bigger than
those on smaller hosts) not only works in a multispecies comparison but also within a single host–single parasite system as
well. 相似文献
90.
Czerwińska E Marcinowska-Suchowierska E Walicka M Lisik W Wierzbicki Z 《Endokrynologia Polska》2007,58(2):130-138
INTRODUCTION: Obese patients may have abnormal calcium homeostasis because of unbalanced diet and decreased sun exposure. Bariatric surgery itself may lead to disturbances in calcium homeostasis (and in consequence changes in bone mass) or increase preexisting metabolic derangements. The aim of the study was: 1. To assess calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity. 2. To determine the impact of bariatric surgery on parameters mentioned above. 3. To establish recommendations for supplementation with calcium and vitamin D in morbidly obese patients after bariatric surgery. MATERIAL AND METHODS: Serum calcium, parathormone (PTH), vitamin D (25(OH)D), biochemical markers of bone turnover (beta-CrossLaps as a marker of bone resorption and osteocalcin as a marker of bone formation) and urine calcium as well as fat mass, lean mass and bone mineral content (by DXA) were measured before bariatric surgery of the stomach (VBG or GBP) in 57 morbidly obese patients (48 women, 9 men; mean age 35.9 y). The same procedures were repeated six months after operation in 28 of them (24 women, 4 men). Daily calcium intake was also determined based on food questionnaire. RESULTS: Biochemical findings in the group of patients before bariatric surgery were as follows: serum calcium, beta-CrossLaps and urine calcium were within normal range, PTH concentration was increased to 81.0 pg/ml and 25(OH)D as well as osteocalcin concentration decreased (4.9 ng/ml and 13.6 ng/ml, respectively). Six months after bariatric surgery there was no change in serum and urine calcium, PTH concentration decreased to normal level (46.8 pg/ml), 25(OH)D concentration increased to 6.5 ng/ml (not significant) and still remained below normal range. Markers of bone turnover--both resorption and formation--increased (beta-CrossLaps over normal range to 0.594 ng/ml, osteocalcin to normal range 26.8 ng/ml). Daily calcium intake was below RDA before and after bariatric procedure. CONCLUSIONS: 1. Patients with morbid obesity have secondary hyperparathyroidism and deficiency of vitamin D. 2. Abrupt weight loss after bariatric surgery is accompanied by the regression of secondary hyperparathyroidism, decrease of the deficiency of vitamin D and increase in bone turnover. 3. Supplementation with vitamin D and calcium is recommended for patients with morbid obesity after bariatric surgery. 相似文献