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31.
32.
Malaria-specific transgenic CD4(+) T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance 总被引:6,自引:0,他引:6
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Stephens R Albano FR Quin S Pascal BJ Harrison V Stockinger B Kioussis D Weltzien HU Langhorne J 《Blood》2005,106(5):1676-1684
T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4(+) T cells expand and produce interferon gamma (IFN-gamma) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4(+) cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine. 相似文献
33.
Frank Ulrich Weiss Nico Hesselbarth Andrea Párniczky Dora Mosztbacher Felix Lämmerhirt Claudia Ruffert Peter Kovacs Sebastian Beer Katharina Seltsam Heidi Griesmann Richard Böhme Tom Kaune Marcus Hollenbach Hans-Ulrich Schulz Peter Simon Julia Mayerle Markus M. Lerch Giulia Martina Cavestro Jonas Rosendahl 《Pancreatology》2018,18(5):477-481
Background/Objectives
Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP.Methods
We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses.Results
Meta-analyses of all AP patients depicted significant (p-value?<?0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81–0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07–1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12–1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63–0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07–1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07–1.93, p-value 0.02) in the alcoholic sub-group only.Conclusions
The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP. 相似文献34.
Philip Konietzke Mark O. Wielptz Willi L. Wagner Felix Wuennemann Hans-Ulrich Kauczor Claus P. Heussel Monika Eichinger Ralf Eberhardt Daniela Gompelmann Oliver Weinheimer 《European radiology》2020,30(5):2502-2512
Chronic obstructive pulmonary disease (COPD) is characterized by variable contributions of emphysema and airway disease on computed tomography (CT), and still little is known on their temporal evolution. We hypothesized that quantitative CT (QCT) is able to detect short-time changes in a cohort of patients with very severe COPD. Two paired in- and expiratory CT each from 70 patients with avg. GOLD stage of 3.6 (mean age = 66 ± 7.5, mean FEV1/FVC = 35.28 ± 7.75) were taken 3 months apart and analyzed by fully automatic software computing emphysema (emphysema index (EI), mean lung density (MLD)), air-trapping (ratio expiration to inspiration of mean lung attenuation (E/I MLA), relative volume change between − 856 HU and − 950 HU (RVC856–950)), and parametric response mapping (PRM) parameters for each lobe separately and the whole lung. Airway metrics measured were wall thickness (WT) and lumen area (LA) for each airway generation and the whole lung. The average of the emphysema parameters (EI, MLD) increased significantly by 1.5% (p < 0.001) for the whole lung, whereas air-trapping parameters (E/I MLA, RVC856–950) were stable. PRMEmph increased from 34.3 to 35.7% (p < 0.001), whereas PRMNormal decrased from 23.6% to 22.8% (p = 0.012). WT decreased significantly from 1.17 ± 0.18 to 1.14 ± 0.19 mm (p = 0.036) and LA increased significantly from 25.08 ± 4.49 to 25.84 ± 4.87 mm2 (p = 0.041) for the whole lung. The generation-based analysis showed heterogeneous results. QCT detects short-time progression of emphysema in severe COPD. The changes were partly different among lung lobes and airway generations, indicating that QCT is useful to address the heterogeneity of COPD progression.
• QCT detects short-time progression of emphysema in severe COPD in a 3-month period.
• QCT is able to quantify even slight parenchymal changes, which were not detected by spirometry.
• QCT is able to address the heterogeneity of COPD, revealing inconsistent changes individual lung lobes and airway generations. 相似文献
35.
Stephanie Kullmann Julia Hummel Robert Wagner Corinna Dannecker Andreas Vosseler Louise Fritsche Ralf Veit Konstantinos Kantartzis Jürgen Machann Andreas L. Birkenfeld Norbert Stefan Hans-Ulrich Hring Andreas Peter Hubert Preissl Andreas Fritsche Martin Heni 《Diabetes care》2022,45(2):398
OBJECTIVEInsulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since sodium–glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance.RESEARCH DESIGN AND METHODSIn this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age 60 ± 9 years; BMI 31.5 ± 3.8 kg/m2) with prediabetes were randomized to receive 25 mg empagliflozin every day or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain.RESULTSWe identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin-treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated the empagliflozin-induced decrease in fasting glucose and liver fat.CONCLUSIONSOur results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism. 相似文献
36.
37.
Mina Kalantari Alejandro Garcia-Carranca Claudia Dalia Morales-Vazquez Rosemary Zuna Delia Perez Montiel Itzel E. Calleja-Macias Bo Johansson Sonia Andersson Hans-Ulrich Bernard 《Virology》2009,390(2):184-163
Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics. 相似文献
38.
Markus Morawski Maike Hartlage-Rübsamen Carsten Jäger Alexander Waniek Stephan Schilling Claudia Schwab Patrick L. McGeer Thomas Arendt Hans-Ulrich Demuth Steffen Roßner 《Acta neuropathologica》2010,120(2):195-207
Glutaminyl cyclase (QC) was discovered recently as the enzyme catalyzing the pyroglutamate (pGlu or pE) modification of N-terminally
truncated Alzheimer’s disease (AD) Aβ peptides in vivo. This modification confers resistance to proteolysis, rapid aggregation
and neurotoxicity and can be prevented by QC inhibitors in vitro and in vivo, as shown in transgenic animal models. However,
in mouse brain QC is only expressed by a relatively low proportion of neurons in most neocortical and hippocampal subregions.
Here, we demonstrate that QC is highly abundant in subcortical brain nuclei severely affected in AD. In particular, QC is
expressed by virtually all urocortin-1-positive, but not by cholinergic neurons of the Edinger–Westphal nucleus, by noradrenergic
locus coeruleus and by cholinergic nucleus basalis magnocellularis neurons in mouse brain. In human brain, QC is expressed
by both, urocortin-1 and cholinergic Edinger–Westphal neurons and by locus coeruleus and nucleus basalis Meynert neurons.
In brains from AD patients, these neuronal populations displayed intraneuronal pE-Aβ immunoreactivity and morphological signs
of degeneration as well as extracellular pE-Aβ deposits. Adjacent AD brain structures lacking QC expression and brains from
control subjects were devoid of such aggregates. This is the first demonstration of QC expression and pE-Aβ formation in subcortical
brain regions affected in AD. Our results may explain the high vulnerability of defined subcortical neuronal populations and
their central target areas in AD as a consequence of QC expression and pE-Aβ formation. 相似文献
39.
Adrien Daigeler Ludger Klein-Hitpass Ansgar Michael Chromik Oliver Müller Jörg Hauser Heinz-Herbert Homann Hans-Ulrich Steinau Marcus Lehnhardt 《BMC cancer》2008,8(1):313
Background
Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. 相似文献40.
Reduced Neutrophil Sequestration in Lung Tissue after
Laparoscopic Lavage in a Rat Peritonitis Model 总被引:4,自引:0,他引:4
Pross M Mantke R Kunz D Reinheckel T Halangk W Lippert H Schulz HU 《World journal of surgery》2002,26(1):49-53
Laparoscopy to treat abdominal infections is becoming more and more popular. The effects of the CO(2) pneumoperitoneum have not yet been completely clarified. In a rat peritonitis model, therefore, we investigated the influence of laparoscopic lavage in comparison with the conventional technique. A defined multibacterial fecal specimen was installed in the abdominal cavities of 80 rats. These animals were randomized to three groups: group 1 (n = 32), no intervention; group 2 (n = 24), conventional; group 3 (n = 24), laparoscopic lavage. At 1, 2, and 8 hours after the surgical intervention, animals were killed and autopsied. The main outcome measures were bacteremia, interleukin-6 (IL-6) in plasma and ascites, changes in the blood count, and myeloperoxidase (MPO) activity in lung, liver, kidney, and pancreas. Differences of bacteremia were not found. In the ascites a marked increase in IL-6 was observed after 8 hours, which was lower in the treatment groups than in the controls (p <0.025). MPO activity as a measure of the granulocytes present in the tissue showed significant changes only in lung tissue. Two hours after the surgical intervention, the MPO in the lung in the laparoscopy group was significantly lower than that in the controls and the laparotomy group. In conclusion, conventional and laparoscopic lavage reduce inflammation. In this model, laparoscopic lavage with a CO(2) pneumoperitoneum appeared to have no negative influence on the inflammatory reaction during the early postoperative phase. Reduced neutrophil sequestration in lung tissue following laparoscopic lavage reflects the lower level of trauma caused by laparoscopy. 相似文献