全文获取类型
收费全文 | 380篇 |
免费 | 26篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 3篇 |
2018年 | 12篇 |
2017年 | 7篇 |
2016年 | 12篇 |
2015年 | 21篇 |
2014年 | 22篇 |
2013年 | 18篇 |
2012年 | 26篇 |
2011年 | 31篇 |
2010年 | 21篇 |
2009年 | 16篇 |
2008年 | 23篇 |
2007年 | 31篇 |
2006年 | 23篇 |
2005年 | 16篇 |
2004年 | 27篇 |
2003年 | 19篇 |
2002年 | 12篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1973年 | 4篇 |
1966年 | 1篇 |
排序方式: 共有406条查询结果,搜索用时 156 毫秒
121.
Daniela Chieffo Claudia Brogna Angela Berardinelli Grazia D’Angelo Maria Mallardi Adele D’Amico Paolo Alfieri Eugenio Mercuri Marika Pane 《PloS one》2015,10(8)
Objective
Neurodevelopmental and cognitive difficulties are known to occur frequently in boys with Duchenne muscular dystrophy but so far none of the published studies have reported both early neurodevelopmental assessments and cognitive tests in the same cohort. The aim of the present longitudinal study was to establish the correlation between early neurodevelopmental assessments performed in preschool boys and the cognitive scales performed at school age or later.Methods
We performed cognitive tests at school age (mean age 5.7 year ±1.7 SD) (69 months+19 SD) in a cohort of Duchenne boys, previously assessed using the Griffiths scales before the age of 4 years (mean age when the Griffiths scales were performed 30 months ±8.9 SD).Results
The range of total Developmental quotients on the Griffiths ranged between 56 and 116 (mean 89 ± 15.6 SD). The total Intelligence Quotients on the Wechsler scales ranged between 35 and 119 (mean 87 ± 17.2 SD). There was a significant correlation between the findings on the two scales. P = <0.0001. When we subdivided the cohort according to site of mutations, there was a difference between boys with mutations upstream exon 44 and those with mutations in exon 44–45 affecting Dp140 on both Developmental and Intelligence Quotient (p 0.01 and p 0,003 respectively).Conclusions
Our results confirm that Duchenne boys tend to slightly underperform on both neurodevelopmental and cognitive assessments. Early neurodevelopmental findings correlated with the cognitive results obtained at school age with a clear concordance between subscales exploring similar domains on the two scales. 相似文献122.
Michele Ferrara Anna Bottasso Daniela Tempesta Marika Carrieri Luigi De Gennaro Giovanni Ponti 《PloS one》2015,10(3)
Excessive working hours—even at night—are becoming increasingly common in our modern 24/7 society. The prefrontal cortex (PFC) is particularly vulnerable to the effects of sleep loss and, consequently, the specific behaviors subserved by the functional integrity of the PFC, such as risk-taking and pro-social behavior, may be affected significantly. This paper seeks to assess the effects of one night of sleep deprivation on subjects’ risk and social preferences, which are probably the most explored behavioral domains in the tradition of Experimental Economics. This novel cross-over study employs thirty-two university students (gender-balanced) participating to 2 counterbalanced laboratory sessions in which they perform standard risk and social preference elicitation protocols. One session was after one night of undisturbed sleep at home, and the other was after one night of sleep deprivation in the laboratory. Sleep deprivation causes increased sleepiness and decreased alertness in all subjects. After sleep loss males make riskier decisions compared to the rested condition, while females do the opposite. Females likewise show decreased inequity aversion after sleep deprivation. As for the relationship between cognitive ability and economic decisions, sleep deprived individuals with higher cognitive reflection show lower risk aversion and more altruistic behavior. These results show that one night of sleep deprivation alters economic behavior in a gender-sensitive way. Females’ reaction to sleep deprivation, characterized by reduced risky choices and increased egoism compared to males, may be related to intrinsic psychological gender differences, such as in the way men and women weigh up probabilities in their decision-making, and/or to the different neurofunctional substrate of their decision-making. 相似文献
123.
Jennifer Jung Heide Marika Genau Christian Behrends 《Molecular and cellular biology》2015,35(14):2479-2494
The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues, such as nutrient status and energy level. Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth. Here, we identify the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex. SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 activity in the presence of amino acids and in response to amino acid replenishment following starvation. Conversely, SLC38A9 overexpression causes RHEB (Ras homolog enriched in brain) GTPase-dependent hyperactivation of mTORC1 and partly sustains mTORC1 activity upon amino acid deprivation. Intriguingly, during amino acid starvation mTOR is retained at the lysosome upon SLC38A9 depletion but fails to be activated. Together, the findings of our study reveal SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to mTORC1 activity. 相似文献
124.
Lise Graversen Thorkild I. A. S?rensen Liselotte Petersen Ulla Sovio Marika Kaakinen Annelli Sandb?k Jaana Laitinen Anja Taanila Anneli Pouta Marjo-Riitta J?rvelin Carsten Obel 《PloS one》2014,9(4)
Background
Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic.Objective
We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic.Methods
We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985–1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2–5 years). We used internal references in early childhood to define percentiles of body size (<50, 50–75, 75–90 and >90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years.Results
The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts.Conclusions
The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice. 相似文献125.
126.
Sreenivasan VK Stremovskiy OA Kelf TA Heblinski M Goodchild AK Connor M Deyev SM Zvyagin AV 《Bioconjugate chemistry》2011,22(9):1768-1775
Somatostatin (SST) is a peptide neurotransmitter/hormone found in several mammalian tissue types. Apart from its natural importance, labeled SST/analogues are utilized in clinical applications such as targeting/diagnosis of neuroendocrine tumors. We report on the development and characterization of a novel, recombinant, fluorescent somatostatin analogue that has potential to elucidate somatostatin-activated cell signaling. SST was genetically fused with a monomeric-red fluorescent protein (mRFP) as the fluorescent label. The attachment of SST to mRFP had no detectable effect on its fluorescent properties. This analogue's potency to activate the endogenous and transfected somatostatin receptors was characterized using assays of membrane potential and Ca(2+) mobilization and immunocytochemistry. SST-mRFP was found to be an effective somatostatin receptor agonist, able to trigger the membrane hyperpolarization, mobilization of the intracellular Ca(2+) and receptor-ligand internalization in cells expressing somatostatin receptors. This complex represents a novel optical reporter due to its red emission spectral band suitable for in vivo imaging and tracking of the somatostatin receptor signaling pathways, affording higher resolution and sensitivity than those of the state-of-the-art radiolabeling bioassays. 相似文献
127.
Gutierrez M Salaffi F Carotti M Tardella M Pineda C Bertolazzi C Bichisecchi E Filippucci E Grassi W 《Arthritis research & therapy》2011,13(4):R134
Introduction
Interstitial pulmonary fibrosis (IPF) is a frequent manifestation in patients with connective tissue disorders (CTD). Recently the ultrasound (US) criterion validity for its assessment has been proposed; however, the US scoring systems adopted include the study of several lung intercostal spaces (LIS), which could be time-consuming in daily clinical practice. The aim of this study was to investigate the utility of a simplified US B-lines scoring system compared with both the US comprehensive assessment and the high-resolution computed tomography (HRCT) findings of IPF in CTD patients. 相似文献128.
Sovio U Mook-Kanamori DO Warrington NM Lawrence R Briollais L Palmer CN Cecil J Sandling JK Syvänen AC Kaakinen M Beilin LJ Millwood IY Bennett AJ Laitinen J Pouta A Molitor J Davey Smith G Ben-Shlomo Y Jaddoe VW Palmer LJ Pennell CE Cole TJ McCarthy MI Järvelin MR Timpson NJ;Early Growth Genetics Consortium 《PLoS genetics》2011,7(2):e1001307
An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p?=?10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p?=?10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p?=?0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p?=?0.01), and earlier AR (-4.72% (-5.81, -3.63), p?=?10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk. 相似文献
129.
130.
Kilpeläinen TO Qi L Brage S Sharp SJ Sonestedt E Demerath E Ahmad T Mora S Kaakinen M Sandholt CH Holzapfel C Autenrieth CS Hyppönen E Cauchi S He M Kutalik Z Kumari M Stančáková A Meidtner K Balkau B Tan JT Mangino M Timpson NJ Song Y Zillikens MC Jablonski KA Garcia ME Johansson S Bragg-Gresham JL Wu Y van Vliet-Ostaptchouk JV Onland-Moret NC Zimmermann E Rivera NV Tanaka T Stringham HM Silbernagel G Kanoni S Feitosa MF Snitker S Ruiz JR Metter J Larrad MT Atalay M Hakanen M Amin N 《PLoS medicine》2011,8(11):e1001116