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1.
Md Maksudul Alam Janmaris Marin Fermin Patrick T. Spiller Chaning Burnett Xiaohua Rong Tara Moore-Medlin Caden O. Maxwell Alok R. Khandelwal Cherie-Ann O. Nathan 《Molecular carcinogenesis》2022,61(1):33-44
TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC. 相似文献
2.
Li Bai Saeha Shin Richard T. Burnett Jeffrey C. Kwong Perry Hystad Aaron van Donkelaar Mark S. Goldberg Eric Lavigne Scott Weichenthal Randall V. Martin Ray Copes Alexander Kopp Hong Chen 《International journal of cancer. Journal international du cancer》2020,146(9):2450-2459
Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2) and ozone (O3). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM2.5, NO2, O3 and redox-weighted average of NO2 and O3 (Ox) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m3) and NO2 (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox. Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer. 相似文献
3.
Alessandro Beneduce MD Cristina Capogrosso MD Francesco Moroni MD Francesco Ancona MD Giulio Falasconi MD Luigi Pannone MD Stefano Stella MD Giacomo Ingallina MD Francesco Melillo MD Marco Bruno Ancona MD Vittorio Romano RT Anna Palmisano MD Azeem Latib MD Antonio Colombo MD Matteo Montorfano MD Antonio Esposito MD Eustachio Agricola MD 《Echocardiography (Mount Kisco, N.Y.)》2020,37(12):2071-2081
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Mohammed C Ben Rayana Robert W Burnett Arthur K Covington Paul D'Orazio Niels Fogh-Andersen Ellis Jacobs Wolf R Külpmann Katsuhiko Kuwa Lasse Larsson Andrzej Lewenstam Anton H J Maas Gerhard Mager Jerzy H J Naskalski Anthony O Okorodudu Christoph Ritter Andrew St John 《Clinical chemistry and laboratory medicine》2005,43(5):564-569
All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium. 相似文献
8.
Cicek MS Lindor NM Gallinger S Bapat B Hopper JL Jenkins MA Young J Buchanan D Walsh MD Le Marchand L Burnett T Newcomb PA Grady WM Haile RW Casey G Plummer SJ Krumroy LA Baron JA Thibodeau SN 《The Journal of molecular diagnostics : JMD》2011,13(3):271-281
The detection of defective mismatch repair (MMR), as assessed by the presence of tumor microsatellite instability (MSI) and/or loss of MMR protein expression by IHC, has been useful for risk assessment, prognosis, and prediction of treatment in patients with colorectal cancer. We analyzed tumors for the presence of defective MMR from 5927 Colorectal Cancer Family Registry patients recruited at six international consortium sites. We evaluated the appropriate percentage instability cutoff used to distinguish the three MSI phenotypes [ie, stable (MSS), low instability (MSI-L), and high instability (MSI-H)]; the sensitivity, specificity, and performance characteristics of individual markers; and the concordance between MSI and IHC phenotypes. Guided by the results of the IHC testing, our findings indicate that the distinction between an MSI-H phenotype from a low-instability or MSS phenotype can best be accomplished by using a cutoff of 30% or greater of the markers showing instability. The sensitivity and specificity of the mononucleotide markers were higher than those of the dinucleotide markers. Specifically, BAT26 and BAT25 had the highest sensitivity (94%) and specificity (98%), and the use of mononucleotide markers alone identified 97% of the MSI-H cases correctly. As expected, the presence of MSI-H correlated with an older age of diagnosis, the presence of tumor in the proximal colon, and female sex. 相似文献
9.
Franck Billmann Therezia Bokor-Billmann Claude Burnett Erhard Kiffner 《World journal of surgery》2013,37(8):1988-1995
Background
The odontoid lateral mass interspace (OLMI) is the space between the lateral aspect of the dens axis and the medial circumference of the massa lateralis atlantis. The position of OLMI asymmetry as a normal variant or pathologic finding is an area of debate and clinical interest in trauma patients. We designed this prospective study to lay a framework for proposing strategies for the appropriate use of OLMI.Methods
A total of 301 adult patients admitted for trauma were included. Computed tomography (CT) and magnetic resonance imaging (MRI) of the cervical spine were performed and examined for the presence OLMI asymmetry and bony/ligamentous lesions of the occipitoatlantoaxial complex.Results
Head rotation is linked to the occurrence of OLMI asymmetry. Reliable OLMI asymmetry evaluation is limited by observer agreement under a threshold value of 1.0 mm. In all, 86 patients (28.6 %) were found to have OLMI asymmetry on CT after trauma. Among these patients, 17.4 % had a bony/ligamentous lesion of the occipitoatlantoaxial complex. Among the patients without OLMI asymmetry, 8.8 % were found to have such lesions.Conclusions
OLMI asymmetry should only be investigated by CT scans of the head in optimal position and with the threshold value of 1.0 mm. OLMI asymmetry should not be used alone as a sign of a cervical spine lesion. MRI should be performed if: (1) the physician has a high degree of suspicion of a cervical spine lesion; (2) OLMI asymmetry was demonstrated on a technically adequate CT scan; (3) clinical symptoms persist in patients with OLMI asymmetry when no acute MRI was performed. 相似文献10.
Hooper AJ van Bockxmeer FM Burnett JR 《Critical reviews in clinical laboratory sciences》2005,42(5-6):515-545
The study of apolipoprotein (apo) B metabolism is central to our understanding of human lipoprotein metabolism. Moreover, the assembly and secretion of apoB-containing lipoproteins is a complex process. Increased plasma concentrations of apoB-containing lipoproteins are an important risk factor for the development of atherosclerotic coronary heart disease. In contrast, decreased levels of, but not the absence of, these apoB-containing lipoproteins is associated with resistance to atherosclerosis and potential long life. The study of inherited monogenic dyslipidaemias has been an effective means to elucidate key metabolic steps and biologically relevant mechanisms. Naturally occurring gene mutations in affected families have been useful in identifying important domains of apoB and microsomal triglyceride transfer protein (MTP) governing the metabolism of apoB-containing lipoproteins. Truncation-causing mutations in the APOB gene cause familial hypobetalipoproteinaemia, whereas mutations in MTP result in abetalipoproteinaemia; both rare conditions are characterised by marked hypocholesterolaemia. The purpose of this review is to examine the role of apoB in lipoprotein metabolism and to explore the key biochemical, clinical, metabolic and genetic features of the monogenic hypocholesterolaemic lipid disorders affecting apoB metabolism. 相似文献