全文获取类型
收费全文 | 490篇 |
免费 | 27篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 14篇 |
2016年 | 11篇 |
2015年 | 20篇 |
2014年 | 30篇 |
2013年 | 21篇 |
2012年 | 50篇 |
2011年 | 37篇 |
2010年 | 15篇 |
2009年 | 17篇 |
2008年 | 39篇 |
2007年 | 28篇 |
2006年 | 29篇 |
2005年 | 23篇 |
2004年 | 23篇 |
2003年 | 16篇 |
2002年 | 20篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 2篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有517条查询结果,搜索用时 687 毫秒
171.
Notari S Mancone C Alonzi T Tripodi M Narciso P Ascenzi P 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,863(2):249-257
The interest in therapeutic drug monitoring (TDM) of antiretroviral drugs has grown significantly since highly active antiretroviral therapy (HAART) became a standard of care in clinical practice. TDM is useful to determine the best dosage regimen adapted to each patient. Here, we apply MALDI-TOF/TOF technology to quantify abacavir, amprenavir, didanosine, efavirenz, nevirapine, and stavudine in the plasma of HIV-infected patients, by standard additions analysis. Regression of standard additions was linear over the whole anti-HIV concentration range explored (1.00 x 10(-2)-1.00 pmol/microL). The absolute recovery ranged between 80% and 110%. Values of the drug concentration determined by MALDI-TOF/TOF were in the range of 1.00 x 10(-2)-1.00 pmol/microL. The limit of quantification value was 1.00 x 10(-2)pmol/microL for abacavir, amprenavir, didanosine, efavirenz, nevirapine, and stavudine. 相似文献
172.
Mantini D Petrucci F Del Boccio P Pieragostino D Di Nicola M Lugaresi A Federici G Sacchetta P Di Ilio C Urbani A 《Bioinformatics (Oxford, England)》2008,24(1):63-70
MOTIVATION: Independent component analysis (ICA) is a signal processing technique that can be utilized to recover independent signals from a set of their linear mixtures. We propose ICA for the analysis of signals obtained from large proteomics investigations such as clinical multi-subject studies based on MALDI-TOF MS profiling. The method is validated on simulated and experimental data for demonstrating its capability of correctly extracting protein profiles from MALDI-TOF mass spectra. RESULTS: The comparison on peak detection with an open-source and two commercial methods shows its superior reliability in reducing the false discovery rate of protein peak masses. Moreover, the integration of ICA and statistical tests for detecting the differences in peak intensities between experimental groups allows to identify protein peaks that could be indicators of a diseased state. This data-driven approach demonstrates to be a promising tool for biomarker-discovery studies based on MALDI-TOF MS technology. AVAILABILITY: The MATLAB implementation of the method described in the article and both simulated and experimental data are freely available at http://www.unich.it/proteomica/bioinf/. 相似文献
173.
Favilla M Pascale M Ricelli A Evidente A Amalfitano C Altomare C 《Applied and environmental microbiology》2008,74(7):2248-2253
Fusapyrone (FP), an antifungal natural compound, was tested against the three main ochratoxigenic species of the Aspergillus section Nigri. The MICs at 24 h were 6.0, 11.6, and 9.9 mug/ml for Aspergillus carbonarius, Aspergillus tubingensis, and Aspergillus niger, respectively. Strong inhibition of growth and morphological changes were still observed at half the MIC after 7 days. The application of a 100 mug/ml FP solution in a laboratory assay on artificially inoculated grapes resulted in a significant reduction (up to 6 orders of magnitude) of A. carbonarius CFU counts. Dramatic reductions of the ochratoxin A (OTA) content, compared to the content of the positive control (average amount of OTA, 112.5 ng/g of grape; three experiments), were obtained with the application of either 100 or 50 mug/ml of FP (0.6 or 5.1 ng/g of grape, respectively). 相似文献
174.
Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Saveria Femminò Carmine Rocca Tommaso Angelone Maria C. Cerra Maria Pia Gallo Iacopo Gesmundo Alessandro Fanciulli Maria Felice Brizzi Pasquale Pagliaro Riccarda Granata 《Journal of cellular and molecular medicine》2017,21(12):3670-3678
Patients with ischaemic heart disease or chronic heart failure show altered levels of obestatin, suggesting a role for this peptide in human heart function. We have previously demonstrated that GH secretagogues and the ghrelin gene‐derived peptides, including obestatin, exert cardiovascular effects by modulating cardiac inotropism and vascular tone, and reducing cell death and contractile dysfunction in hearts subjected to ischaemia/reperfusion (I/R), through the Akt/nitric oxide (NO) pathway. However, the mechanisms underlying the cardiac actions of obestatin remain largely unknown. Thus, we suggested that obestatin‐induced activation of PI3K/Akt/NO and PKG signalling is implicated in protection of the myocardium when challenged by adrenergic, endothelinergic or I/R stress. We show that obestatin exerts an inhibitory tone on the performance of rat papillary muscle in both basal conditions and under β‐adrenergic overstimulation, through endothelial‐dependent NO/cGMP/PKG signalling. This pathway was also involved in the vasodilator effect of the peptide, used both alone and under stress induced by endothelin‐1. Moreover, when infused during early reperfusion, obestatin reduced infarct size in isolated I/R rat hearts, through an NO/PKG pathway, comprising ROS/PKC signalling, and converging on mitochondrial ATP‐sensitive potassium [mitoK(ATP)] channels. Overall, our results suggest that obestatin regulates cardiovascular function in stress conditions and induces cardioprotection by mechanisms dependent on activation of an NO/soluble guanylate cyclase (sGC)/PKG pathway. In fact, obestatin counteracts exaggerated β‐adrenergic and endothelin‐1 activity, relevant factors in heart failure, suggesting multiple positive effects of the peptide, including the lowering of cardiac afterload, thus representing a potential candidate in pharmacological post‐conditioning. 相似文献
175.
Dino Cancemi Alessandra Iannuzzi Angela Perucatti Luigi Montano Oronzo Capozzi Carmine Spampanato Maria Luisa Ventruto Maria Urciuoli Leopoldo Iannuzzi Valerio Ventruto 《Journal of applied genetics》2017,58(4):481-486
Duplications of Yq arm (and AZF) seems to be tolerated by fertile males, while mutations, deletions, duplications or haploinsufficiency of SHOX can originate a wide range of phenotypes, including short stature and skeletal abnormalities. We report a case of non-obstructive azoospermia in a young man with short stature, skeletal anomalies, normal intelligence and hormonal parameters. This male showed a very singular Y-chromosome aberration, consisting of a duplication of Yq and proximal regions of Yp, with a deletion of almost all PAR1 in Yptel, including SHOX. CBA- and RBA-banding and FISH-mapping with telomeric, centromeric, AZF and SHOX probes were used. These results were confirmed by array CGH, which revealed the following karyotype constitution: arr [hg19] Xp22.33 or Yp11.32p11.31 (310,932–2,646,815 or 260,932–2,596,815) ×1, Yp11.2q12 (8,641,183–59,335,913) ×2. We conclude that the haploinsufficience of SHOX may be the cause of short stature and skeletal defects in the patient, while the non-obstructive azoospermia could be related to the lack of X–Y pairing during meiosis originated by the anomalous configuration of this chromosome abnormality and large deletion which occurred in Yp-PAR1. 相似文献
176.
Emanuela Galliera Monica Gioia Marazzi Carmine Gazzaruso Pietro Gallotti Adriana Coppola Tiziana Montalcini Arturo Pujia Massimiliano M. Corsi Romanelli 《Immunity & ageing : I & A》2017,14(1):13
Background
Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism.Results
Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism.Conclusions
The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.177.
Carmine Gazzaruso Adriana Garzaniti Stefano Giordanetti Colomba Falcone Pietro Fratino 《Cardiovascular diabetology》2002,1(1):5-9
Background
There is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD) in diabetic patients. We investigated whether Lipoprotein(a), homocysteine and apolipoprotein(a) polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD) in diabetic patients. 相似文献178.
P A Farrell M J Fedele J Hernandez J D Fluckey J L Miller C H Lang T C Vary S R Kimball L S Jefferson 《Journal of applied physiology》1999,87(3):1075-1082
This study had the following objectives: 1) to determine whether diabetic rats could increase muscle mass due to a physiological manipulation (chronic resistance exercise), 2) to determine whether exercise training status modifies the effect of the last bout of exercise on elevations in rates of protein synthesis, and 3) to determine whether chronic resistance exercise alters basal glycemia. Groups consisted of diabetic or nondiabetic rats that performed progressive resistance exercise for 8 wk, performed acute resistance exercise, or remained sedentary. Arterial plasma insulin in diabetic groups was reduced by about one-half (P < 0.05) compared with nondiabetic groups. Soleus and gastrocnemius-plantaris complex muscle wet weights were lower because of diabetes, but in response to chronic exercise these muscles hypertrophied in diabetic (0.028 +/- 0.003 vs. 0.032 +/- 0.0015 g/cm for sedentary vs. exercised soleus and 0.42 +/- 0.068 vs. 0.53 +/- 0.041 g/cm for sedentary vs. exercised gastrocnemius-plantaris, both P < 0.05) but not in nondiabetic (0.041 +/- 0.0026 vs. 0.042 +/- 0.003 g/cm for sedentary vs. exercised soleus and 0.72 +/- 0.015 vs. 0.69 +/- 0.013 g/cm for sedentary vs. exercised gastrocnemius-plantaris) rats when muscle weight was expressed relative to tibial length or body weight (data not shown). Another group of diabetic rats that lifted heavier weights showed muscle hypertrophy. Rates of protein synthesis were higher in red gastrocnemius in chronically exercised than in sedentary rats: 155 +/- 11 and 170 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in exercised diabetic and nondiabetic rats vs. 110 +/- 14 and 143 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in sedentary diabetic and nondiabetic rats. These elevations, however, were lower than in acutely exercised (but untrained) rats: 176 +/- 15 and 193 +/- 8 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in diabetic and nondiabetic rats. Finally, chronic exercise training in diabetic rats was associated with reductions in basal glycemia, and such reductions did not occur in sedentary diabetic groups. These data demonstrate that, despite lower circulating insulin concentrations, diabetic rats can increase muscle mass in response to a physiological stimulus. 相似文献
179.
Lorenzo Franci Alessandro Tubita Franca Maria Bertolino Alessandro Palma Giuseppe Cannino Carmine Settembre Andrea Rasola Elisabetta Rovida Mario Chiariello 《Aging cell》2022,21(7)
Mitochondria are the major source of reactive oxygen species (ROS), whose aberrant production by dysfunctional mitochondria leads to oxidative stress, thus contributing to aging as well as neurodegenerative disorders and cancer. Cells efficiently eliminate damaged mitochondria through a selective type of autophagy, named mitophagy. Here, we demonstrate the involvement of the atypical MAP kinase family member MAPK15 in cellular senescence, by preserving mitochondrial quality, thanks to its ability to control mitophagy and, therefore, prevent oxidative stress. We indeed demonstrate that reduced MAPK15 expression strongly decreases mitochondrial respiration and ATP production, while increasing mitochondrial ROS levels. We show that MAPK15 controls the mitophagic process by stimulating ULK1‐dependent PRKN Ser108 phosphorylation and inducing the recruitment of damaged mitochondria to autophagosomal and lysosomal compartments, thus leading to a reduction of their mass, but also by participating in the reorganization of the mitochondrial network that usually anticipates their disposal. Consequently, MAPK15‐dependent mitophagy protects cells from accumulating nuclear DNA damage due to mitochondrial ROS and, consequently, from senescence deriving from this chronic DNA insult. Indeed, we ultimately demonstrate that MAPK15 protects primary human airway epithelial cells from senescence, establishing a new specific role for MAPK15 in controlling mitochondrial fitness by efficient disposal of old and damaged organelles and suggesting this kinase as a new potential therapeutic target in diverse age‐associated human diseases. 相似文献