全文获取类型
收费全文 | 6042篇 |
免费 | 418篇 |
国内免费 | 1篇 |
出版年
2023年 | 41篇 |
2022年 | 101篇 |
2021年 | 225篇 |
2020年 | 111篇 |
2019年 | 148篇 |
2018年 | 208篇 |
2017年 | 153篇 |
2016年 | 219篇 |
2015年 | 359篇 |
2014年 | 410篇 |
2013年 | 505篇 |
2012年 | 598篇 |
2011年 | 526篇 |
2010年 | 320篇 |
2009年 | 267篇 |
2008年 | 347篇 |
2007年 | 343篇 |
2006年 | 282篇 |
2005年 | 244篇 |
2004年 | 234篇 |
2003年 | 181篇 |
2002年 | 144篇 |
2001年 | 35篇 |
2000年 | 30篇 |
1999年 | 35篇 |
1998年 | 24篇 |
1997年 | 22篇 |
1996年 | 19篇 |
1995年 | 22篇 |
1994年 | 15篇 |
1993年 | 24篇 |
1992年 | 22篇 |
1991年 | 13篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 11篇 |
1986年 | 8篇 |
1985年 | 27篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 7篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1974年 | 10篇 |
1973年 | 12篇 |
排序方式: 共有6461条查询结果,搜索用时 414 毫秒
91.
Carlo Dani Lucia Giannini Giovanna Bertini Simone Pratesi Iuri Corsini Mariangela Longini 《Free radical research》2013,47(12):1358-1363
The higher risk of respiratory problem in infants delivered by elective caesarean section in comparison with vaginally born infants may be favoured by lower level of nitric oxide (NO) and carbon monoxide (CO) and higher oxidative stress in infants born by caesarean section. We studied healthy term infants born by vaginal delivery or by elective caesarean section. Nitric oxide, CO, guanosine 3–5 cyclic monophosphate, total hydroperoxide and advanced oxidation protein products (AOPP) were measured at birth and 48–72 h of life. Nitric oxide, CO and cGMP were lower at birth and at 48–72 h of life in infants born by elective caesarean delivery. Total hydroperoxide and AOPP levels were similar in the two groups and increased from birth to 48–72 h of life. In conclusion, nitric oxide and CO concentrations were higher in term infants vaginally born than in infants born by elective caesarean section and decreased from birth to 48–72 h of life. The mode of delivery did not affect the oxidative stress which increases from birth to 48–72 h of life. 相似文献
92.
93.
Valentina Gambino Giulia De Michele Oriella Venezia Pierluigi Migliaccio Valentina Dall'Olio Loris Bernard Simone Paolo Minardi Maria Agnese Della Fazia Daniela Bartoli Giuseppe Servillo Myriam Alcalay Lucilla Luzi Marco Giorgio Heidi Scrable Pier Giuseppe Pelicci Enrica Migliaccio 《Aging cell》2013,12(3):435-445
94.
Alessandra Vacca Roberta Montisci Pietro Garau Paolo Siotto Matteo Piga Alberto Cauli Massimo Ruscazio Luigi Meloni Sabino Iliceto Alessandro Mathieu 《Arthritis research & therapy》2013,15(1):R8
Introduction
Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome.Methods
Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up.Results
Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests.Conclusions
A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases. 相似文献95.
Nicola Bizzaro Elena Bartoloni Gabriella Morozzi Stefania Manganelli Valeria Riccieri Paola Sabatini Matteo Filippini Marilina Tampoia Antonella Afeltra Giandomenico Sebastiani Claudia Alpini Vittorio Bini Onelia Bistoni Alessia Alunno Roberto Gerli 《Arthritis research & therapy》2013,15(1):R16
Introduction
The diagnostic, predictive and prognostic role of anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis (RA) patients is widely accepted. Moreover, detection of these antibodies in subjects presenting with undifferentiated arthritis (UA) is associated with a significant risk to develop the disease. On the other hand, clinical and prognostic significance of evaluating anti-CCP levels in subjects with inflammatory arthritis at disease onset has not been fully clarified. The goal of this prospective study is to analyze the value and prognostic significance of anti-CCP titer quantification in UA subjects.Methods
Serial anti-CCP assays were measured in 192 consecutive patients presenting with UA lasting less than 12 weeks. Clinical and serological data and arthritis outcome were evaluated every 6 months until two years of follow-up.Results
Anti-CCP positivity, at both low and high titer, and arthritis of hand joints significantly predicted RA at two years, risk increasing in subjects with high anti-CCP titers at baseline. Moreover, time to RA diagnosis was shorter in patients with high anti-CCP2 titers at enrollment with respect to those with low antibody concentration.Conclusions
Presence of anti-CCP antibodies, at both low and high concentration, is significantly associated with RA development in subjects with recent onset UA. However, time interval from the onset of the first symptoms to the fulfilment of the classification criteria appears to be directly related to the initial anti-CCP level. 相似文献96.
Daniela Nicole Filoni Rossana Pesi Maria Giovanna Careddu Marcella Camici Simone Allegrini Anita Collavoli 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1155-1160
IMP preferring cytosolic 5 ′-nucleotidase II (cN-II) is a widespread enzyme whose amino acid sequence is highly conserved among vertebrates. Fluctuations of its activity have been reported in some pathological conditions and its mRNA levels have been proposed as a prognostic factor for poor outcome in patients with adult acute myeloid leukemia. As a member of the oxypurine cycle, cN-II is involved in the regulation of intracellular concentration of 5′-inosine monophosphate (IMP), 5′-guanosine monophosphate (GMP), and also 5-phosphoribose 1-pyrophosphate (PRPP) and is therefore involved in the regulation of purine and pyrimidine de novo and salvage synthesis. In addition, several studies demonstrated the involvement of cN-II in pro-drug metabolism. Notwithstanding some publications indicating that cN-II is essential for the survival of several cell types, its role in cell metabolism remains uncertain. To address this issue, we built two eucaryotic cellular models characterized by different cN-II expression levels: a constitutive cN-II knockdown in the astrocytoma cell line (ADF) by short hairpin RNA (shRNA) strategy and a cN-II expression in the diploid strain RS112 of Saccharomyces cerevisiae. Preliminary results suggest that cN-II is essential for cell viability, probably because it is directly involved in the regulation of nucleotide pools. These two experimental approaches could be very useful for the design of a personalized chemotherapy. 相似文献
97.
Matteo Tiecco Pietro Di Profio Raimondo Germani Gianfranco Savelli 《Nucleosides, nucleotides & nucleic acids》2013,32(10):911-923
Here we describe uridine functionalization in the 5′ position, which provides new classes of cationic and nonionic amphiphiles specifically designed as DNA transfection agents. The synthetic procedures developed to obtain the cationic uridine-head surfactants prevented intramolecular cyclization that occurs when uridine is functionalized in this position without using protecting groups in the uracil. 相似文献
98.
Christine Bouchardy Harriet Wikman Simone Benhamou Ari Hirvonen Pierre Dayer Kirsti Husgafvel-Pursiainen 《Biomarkers》2013,18(2):131-134
The CYP1A1 gene encoding for an enzyme involved in the metabolic activation of important tobacco carcinogens could be implicated in smoking-induced lung cancer. Given the strong association between tobacco smoking and lung cancer, the effect of tobacco smoke exposure has to be taken into account when studying the potential association between lung cancer and CYP1A1 genotypes. The effect of two CYP1A1 genetic polymorphisms (Mspl and IIe-Val) on lung cancer risk were evaluated using peripheral blood DNA from 150 lung cancer patients and 171 controls. The Mspl sitepresent allele was found among 19.3% of both cases and controls and the variant allele Val among 6.7% of cases and 8.8% of controls. Lung cancer risks associated with the Mspl site-present allele (OR= 0.9; 95%Cl: 0.5-1.8) or with the Val allele (OR= 0.8; 95%Cl: 0.3-1.9) were not increased after adjustment for tobacco and asbestos exposures. These results persisted when analyses were stratified on smoking status, daily consumption of tobacco or duration of smoking. Similar findings were obtained when squamous cell or small cell carcinomas were studied separately. This study thus suggests a minor role for the known CYP1A1 gene polymorphisms in predisposition to lung cancer among Caucasian populations. 相似文献
99.
Katrine A. Gorham Mads P. Sulbaek Andersen Simone Meinardi Ralph J. Delfino Norbert Staimer Thomas Tjoa 《Biomarkers》2013,18(1):17-25
The relationship of exhaled ethane and n-pentane to exhaled NO, carbonylated proteins, and indoor/outdoor atmospheric pollutants were examined in order to evaluate ethane and n-pentane as potential markers of airway inflammation and/or oxidative stress. Exhaled NO and carbonylated proteins were found to have no significant associations with either ethane (p = 0.96 and p = 0.81, respectively) or n-pentane (p = 0.44 and 0.28, respectively) when outliers were included. In the case where outliers were removed n-pentane was found to be inversely associated with carbonylated proteins. Exhaled hydrocarbons adjusted for indoor hydrocarbon concentrations were instead found to be positively associated with air pollutants (NO, NO2 and CO), suggesting pollutant exposure is driving exhaled hydrocarbon concentrations. Given these findings, ethane and n-pentane do not appear to be markers of airway inflammation or oxidative stress. 相似文献
100.
Simone Kreutmayer Adam Csordas Jan Kern Viola Maass Giovanni Almanzar Martin Offterdinger Robert Öllinger Matthias Maass Georg Wick 《Cell stress & chaperones》2013,18(3):259-268
We identified increased expression and redistribution of the intracellular protein 60-kDa human heat shock protein (hHSP60) (HSPD1) to the cell surface in human endothelial cells subjected to classical atherosclerosis risk factors and subsequent immunologic cross-reactivity against this highly conserved molecule, as key events occurring early in the process of atherosclerosis. The present study aimed at investigating the role of infectious pathogens as stress factors for vascular endothelial cells and, as such, contributors to early atherosclerotic lesion formation. Using primary donor-matched arterial and venous human endothelial cells, we show that infection with Chlamydia pneumoniae leads to marked upregulation and surface expression of hHSP60 and adhesion molecules. Moreover, we provide evidence for an increased susceptibility of arterial endothelial cells for redistribution of hHSP60 to the cellular membrane in response to C. pneumoniae infection as compared to autologous venous endothelial cells. We also show that oxidative stress has a central role to play in endothelial cell activation in response to chlamydial infection. These data provide evidence for a role of C. pneumoniae as a potent primary endothelial stressor for arterial endothelial cells leading to enrichment of hHSP60 on the cellular membrane and, as such, a potential initiator of atherosclerosis. 相似文献