全文获取类型
收费全文 | 1620篇 |
免费 | 129篇 |
专业分类
1749篇 |
出版年
2024年 | 1篇 |
2023年 | 13篇 |
2022年 | 20篇 |
2021年 | 38篇 |
2020年 | 25篇 |
2019年 | 31篇 |
2018年 | 50篇 |
2017年 | 34篇 |
2016年 | 61篇 |
2015年 | 84篇 |
2014年 | 91篇 |
2013年 | 124篇 |
2012年 | 138篇 |
2011年 | 126篇 |
2010年 | 91篇 |
2009年 | 73篇 |
2008年 | 101篇 |
2007年 | 88篇 |
2006年 | 89篇 |
2005年 | 88篇 |
2004年 | 67篇 |
2003年 | 73篇 |
2002年 | 70篇 |
2001年 | 14篇 |
2000年 | 7篇 |
1999年 | 15篇 |
1998年 | 22篇 |
1997年 | 10篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 1篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有1749条查询结果,搜索用时 0 毫秒
41.
Dalle Grave R Cuzzolaro M Calugi S Tomasi F Temperilli F Marchesini G;and the QUOVADIS Study Group 《Obesity (Silver Spring, Md.)》2007,15(9):2320-2327
Objective: Body image dissatisfaction is common in treatment‐seeking patients with obesity. We aimed to investigate the effects of obesity management on body image in patients with obesity attending Italian medical centers for weight loss programs. Research Methods and Procedures: A total of 473 obese patients seeking treatment in 13 Italian medical centers (80% females; age, 45.9 ± standard deviation 11.0 years; BMI, 36.8 ± 5.7 kg/m2) were evaluated at baseline and after a 6‐month weight loss treatment. Body uneasiness, psychiatric distress, and binge eating were tested by Body Uneasiness Test (BUT, Part A), Symptom CheckList‐90 (SCL‐90), and Binge Eating Scale (BES), respectively. Results: At 6‐month follow‐up, the percentage weight loss was significantly higher in men (9.0 ± 6.3%) than in women (6.8 ± 7.3%; p = 0.010). Both men and women had a significant improvement in BUT Global Severity Index and in all of the BUT subscales with the exception of the Compulsive Self‐Monitoring subscale. Linear regression analysis selected baseline psychological and behavioral measures (global score of BUT and SCL‐90) and improved psychiatric distress and binge eating as independent predictors of changes in basal body dissatisfaction in females, whereas in males, changes were associated only with baseline BUT‐Global Severity Index score, binge eating, and its treatment‐associated improvement. Pre‐treatment BMI and BMI changes did not enter the regression. Discussion: Obesity treatment, even with a modest degree of weight loss, is associated with a significant improvement of body image, in both females and males. This effect depends mainly on psychological factors, not on the amount of weight loss. 相似文献
42.
Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively. 相似文献
43.
Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines 总被引:1,自引:0,他引:1
Fontana S Alessandro R Barranca M Giordano M Corrado C Zanella-Cleon I Becchi M Kohn EC De Leo G 《Journal of proteome research》2007,6(11):4330-4342
The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment. 相似文献
44.
De Marchi Fabiola De Rosso Mirko Flamini Riccardo 《Metabolomics : Official journal of the Metabolomic Society》2022,18(6):1-6
Metabolomics - Much evidence for diabetes mellitus being associated with dysregulated lipid metabolism has been accrued from studies using blood plasma. However, the systemic dysregulation these... 相似文献
45.
Gerardo Abbandonato Barbara Storti Ilaria Tonazzini Martin Stöckl Vinod Subramaniam Costanza Montis Riccardo Nifosì Marco Cecchini Giovanni Signore Ranieri Bizzarri 《Biophysical journal》2019,116(3):477-486
The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (Lo or lipid raft) and more disordered (Ld) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the Lo and Ld domains in living cells on account of its large fluorescence lifetime variation in the two phases. The domain composition is straightforwardly obtained by the phasor approach to confocal fluorescence lifetime imaging, a graphical method that does not require global fitting of the fluorescence decay in every spatial position of the sample. Our imaging strategy was applied to recover the domain composition in human oligodendrocytes at rest and under treatment with galactosylsphingosine (psychosine). Exogenous psychosine administration recapitulates many of the molecular fingerprints of a severe neurological disease, globoid cell leukodystrophy, better known as Krabbe disease. We found out that psychosine progressively destabilizes plasma membrane, as witnessed by a shrinking of the Lo fraction. The unchanged levels of galactosyl ceramidase, i.e., the enzyme lacking in Krabbe disease, upon psychosine treatment suggest that psychosine alters the plasma membrane structure by direct physical effect, as also recently demonstrated in model membranes. 相似文献
46.
47.
Site-Specific Integration in Mammalian Cells Mediated by a New Hybrid Baculovirus–Adeno-Associated Virus Vector 下载免费PDF全文
Fabio Palombo Andrea Monciotti Alessandra Recchia Riccardo Cortese Gennaro Ciliberto Nicola La Monica 《Journal of virology》1998,72(6):5025-5034
Baculovirus can transiently transduce primary human and rat hepatocytes, as well as a subset of stable cell lines. To prolong transgene expression, we have developed new hybrid vectors which associate key elements from adeno-associated virus (AAV) with the elevated transducing capacity of baculovirus. The hybrid vectors contain a transgene cassette composed of the β-galactosidase (β-Gal) reporter gene and the hygromycin resistance (Hygr) gene flanked by the AAV inverted terminal repeats (ITRs), which are necessary for AAV replication and integration in the host genome. Constructs were derived both with and without the AAV rep gene under the p5 and p19 promoters cloned in different positions with respect to the baculovirus polyheidrin promoter. A high-titer preparation of baculovirus-AAV (Bac-AAV) chimeric virus containing the ITR–Hygr–β-Gal sequence was obtained with insect cells only when the rep gene was placed in an antisense orientation to the polyheidrin promoter. Infection of 293 cells with Bac-AAV virus expressing the rep gene results in a 10- to 50-fold increase in the number of Hygr stable cell clones. Additionally, rep expression determined the localization of the transgene cassette in the aavs1 site in approximately 41% of cases as detected by both Southern blotting and fluorescent in situ hybridization analysis. Moreover, site-specific integration of the ITR-flanked DNA was also detected by PCR amplification of the ITR-aavs1 junction in transduced human fibroblasts. These data indicate that Bac-AAV hybrid vectors can allow permanent, nontoxic gene delivery of DNA constructs for ex vivo treatment of primary human cells. 相似文献
48.
49.
Russo A Filippi C Tombolini R Toffanin A Bedini S Agnolucci M Nuti M 《Microbiological research》2003,158(3):265-270
Pseudomonas sp., (formerly reported as strain P12) which produces brown blotch disease symptoms on Pleurotus eryngii, has been identified as P. tolaasii based on its biochemical, physiological properties and 16S rDNA sequence analysis. This pathogen is able to infect basidiocarps when surface-inoculated on mushroom casing soil. However, infected basidiocarps develop the brown blotch disease symptoms when the pathogen concentration in the fruiting body tissues is higher than 10(4) cfu/g d.w. Using gfp-tagged cells and confocal laser scanning microscopy, it was possible to show that the pathogen has the ability to tightly attach to the hyphae of Pleurotus eryngii. 相似文献
50.
Scheggi S Leggio B Masi F Grappi S Gambarana C Nanni G Rauggi R De Montis MG 《Journal of neurochemistry》2002,83(4):895-903
Stressful events are accompanied by modifications in dopaminergic transmission in distinct brain regions. As the activity of the neuronal dopamine (DA) transporter (DAT) is considered to be a critical mechanism for determining the extent of DA receptor activation, we investigated whether a 3-week exposure to unavoidable stress, which produces a reduction in DA output in the nucleus accumbens shell (NAcS) and medial prefrontal cortex (mPFC), would affect DAT density and DA D1 receptor complex activity in the NAcS, mPFC and caudate-putamen (CPu). Rats exposed to unavoidable stress showed a decreased DA output in the NAcS accompanied by a decrease in the number of DAT binding sites, and an increase in the number of DA D1 binding sites and Vmax of SKF 38393-stimulated adenylyl cyclase. In the mPFC, stress exposure produced a decrease in DA output with no modification in DAT binding or in DA D1 receptor complex activity. Moreover, in the CPu stress exposure induced no changes in DA output or in the other neurochemical variables examined. This study shows that exposure to a chronic unavoidable stress that produces a decrease in DA output in frontomesolimbic areas induced several adaptive neurochemical modifications selectively in the nucleus accumbens. 相似文献