全文获取类型
收费全文 | 1755篇 |
免费 | 134篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 28篇 |
2020年 | 22篇 |
2019年 | 24篇 |
2018年 | 24篇 |
2017年 | 29篇 |
2016年 | 36篇 |
2015年 | 87篇 |
2014年 | 72篇 |
2013年 | 140篇 |
2012年 | 178篇 |
2011年 | 147篇 |
2010年 | 98篇 |
2009年 | 81篇 |
2008年 | 105篇 |
2007年 | 116篇 |
2006年 | 106篇 |
2005年 | 101篇 |
2004年 | 89篇 |
2003年 | 82篇 |
2002年 | 78篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 18篇 |
1998年 | 24篇 |
1997年 | 19篇 |
1996年 | 14篇 |
1995年 | 17篇 |
1994年 | 12篇 |
1993年 | 15篇 |
1992年 | 12篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有1889条查询结果,搜索用时 468 毫秒
911.
Pecci A Biino G Fierro T Bozzi V Mezzasoma A Noris P Ramenghi U Loffredo G Fabris F Momi S Magrini U Pirastu M Savoia A Balduini C Gresele P;Italian Registry for MYH-releated diseases 《PloS one》2012,7(4):e35986
Background
MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance.Methods and Findings
Data concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of 63 (27.0%) an increase of GGT. The increases ranged from 1.9±0.7 to 2.7±1.6 fold the upper normal limit. The prevalence of liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios ranging from 8.2 (95% CIs 2.2–44.8) to 24.7 (14.8–40.8). Clinical follow-up and more detailed liver studies of a subset of patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant structural damage or evolution towards liver insufficiency.Conclusions
Elevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome; however, this defect does not appear to have poor prognostic value. 相似文献912.
Verbeek EC Bakker IM Bevova MR Bochdanovits Z Rizzu P Sondervan D Willemsen G de Geus EJ Smit JH Penninx BW Boomsma DI Hoogendijk WJ Heutink P 《PloS one》2012,7(5):e37384
Major depressive disorder (MDD) is a psychiatric disorder that is characterized--amongst others--by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f.>0.1, r(2)>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P?=?6.8E-7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P?=?1.2E-6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P?=?9.9E-7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833. 相似文献
913.
D'Alessandro A D'Aguanno S Cencioni MT Pieroni L Diamantini A Battistini L Longone P Spalloni A De Laurenzi V Bernardini S Federici G Urbani A 《Journal of Proteomics》2012,75(4):1440-1453
The Ubiquitin-Proteasome System (UPS) and the Autophagy-Lysosome Pathways (ALP) are key mechanisms for cellular homeostasis sustenance and protein clearance. A wide number of Neurodegenerative Diseases (NDs) are tied with UPS impairment and have been also described as proteinopathies caused by aggregate-prone proteins, not efficiently removed by proteasome. Despite the large knowledge on proteasome biological role, molecular mechanisms associated with its impairment are still blur. We have pursued a comprehensive proteomic investigation to evaluate the phenotypic rearrangements in protein repertoires associated with a UPS blockage. Different functional proteomic approaches have been employed to tackle UPS impairment impact on human NeuroBlastoma (NB) cell lines responsive to proteasome inhibition by Epoxomicin. 2-Dimensional Electrophoresis (2-DE) separation combined with Mass Spectrometry and Shotgun Proteomics experiments have been employed to design a thorough picture of protein profile. Unsupervised meta-analysis of the collected proteomic data revealed that all the identified proteins relate each other in a functional network centered on beta-estradiol. Moreover we showed that treatment of cells with beta-estradiol resulted in aggregate removal and increased cell survival due to activation of the autophagic pathway. Our data may provide the molecular basis for the use of beta-estradiol in neurodegenerative disorders by induction of protein aggregate removal. 相似文献
914.
Xianming du Prel Carroll Honggang Yi Yuezhu Liang Ke Pang Sandra Leeper-Woodford Patrizia Riccardi Xianhong Liang 《PloS one》2012,7(11)
Background
Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting an estimated 5 to 12% of school-aged children worldwide. From 15 to 19 million Chinese children suffer from ADHD. The aim of this study was to investigate the association between family-environmental factors and ADHD in a sample of Chinese children.Methods
A pair-matched, case-control study was conducted with 161 ADHD children and 161 non-ADHD children of matching age and sex, all from 5–18 years of age. The ADHD subjects and the normal controls were all evaluated via structured diagnostic interviews. We examined the association between family-environmental factors and ADHD using the conditional multiple logistic regression with backward stepwise selection to predict the associated factors of ADHD.Results
Having experienced emotional abuse and being a single child were both significant factors associated with children diagnosed with ADHD. ADHD subjects were more likely to have suffered from emotional abuse (OR = 11.09, 95% CI = 2.15–57.29, P = 0.004) and have been a single child in the family (OR = 6.32, 95% CI = 2.09–19.14, P = 0.001) when compared to normal controls. The results were not modified by other confounding factors.Conclusion
Our findings provide evidence that family-environmental factors are associated with ADHD among children in China. These findings, if confirmed by future research, may help to decrease ADHD by increasing the awareness of the effects of childhood emotional abuse. 相似文献915.
Falabella P Riviello L Pascale M Lelio ID Tettamanti G Grimaldi A Iannone C Monti M Pucci P Tamburro AM Deeguileor M Gigliotti S Pennacchio F 《Insect biochemistry and molecular biology》2012,42(3):203-211
The innate immune system of insects consists of humoural and cellular responses that provide protection against invading pathogens and parasites. Defence reactions against these latter include encapsulation by immune cells and targeted melanin deposition, which is usually restricted to the surface of the foreign invader, to prevent systemic damage. Here we show that a protein produced by haemocytes of Heliothis virescens (Lepidoptera, Noctuidae) larvae, belonging to XendoU family, generates amyloid fibrils, which accumulate in large cisternae of the rough endoplasmic reticulum and are released upon immune challenge, to form a layer coating non-self objects entering the haemocoel. This amyloid layer acts as a molecular scaffold that promotes localised melanin synthesis and the adhesion of immune cells around the non-self intruder during encapsulation response. Our results demonstrate a new functional role for these protein aggregates that are commonly associated with severe human diseases. We predict that insects will offer new powerful experimental systems for studying inducible amyloidogenesis, which will likely provide fresh perspectives for its prevention. 相似文献
916.
Signaling pathways between mitochondrial and nuclear genomes are activated to preserve cellular homeostasis, especially in the event of stress. Using cybrid cell lines, we investigated whether inherited mitochondrial DNA (mtDNA) variants modulate the expression profiles of mammalian sirtuins (SIRT1-7) under oxidative stress conditions. We found that the expression of the SIRT3 gene was down-regulated in cybrids harboring mtDNA of the J haplogroup, which correlated with mitochondrial function, resulting in a decline of NAD(+)/NADH and ATP levels. Overall, the data reported here highlight a link between SIRT3, mitochondrial DNA variability and mitochondrial functionality, three fundamental components of the cellular stress response. 相似文献
917.
Puglisi R Pozzi A Foglio L Spanò M Eleuteri P Grollino MG Bongioni G Galli A 《Animal reproduction science》2012,132(1-2):17-28
To date, no single in vitro assessment can estimate bull fertility. This research was aimed at evaluating the ability of a series of laboratory assessments to assign 50 Holstein Friesian bulls grouped as low (ER-NRR<-1.5), medium (-0.5相似文献
918.
919.
920.
The distinctive nucleus of kainoid amino acids, (2S,3R)-(+)-2-carboxypyrrolidine-3-acetic acid 6, was synthesized by a chemoenzymatic process, exploiting the diastereomeric cis/trans methyl pyroglutamate derivatives 10a-c/11a-c as key intermediates. These mixtures, when subjected to a kinetic resolution mediated by α-chymotrypsin, reacted diastereo-, regio-, and enantioselectively to give the trans derivatives (+)-10a-c possessing the correct (2S,3R) configuration. Subsequently, the desired product (2S,3R)-(+)-6 could be obtained after well-established transformations. 相似文献