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1.
Claudia Gedlicka Gudrun Hager Martina Weissenböck Wilhelm Gedlicka Birgit Knerer Johannes Kornfehl Michael Formanek 《Journal of oral pathology & medicine》2006,35(8):472-478
BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25. 相似文献
2.
Till Neumann Birgit Ross Ulrich R. Hengge Guido Gerken Raimund Erbel 《Medizinische Klinik》2002,117(3):659-665
Zusammenfassung. Die Infektion mit dem humanen Immundefizienzvirus (HIV) betrifft nicht nur das Immunsystem des menschlichen Organismus, sondern schließt vielmehr eine Reihe weiterer Organsysteme mit ein. Es wird angenommen, dass bei 5-15% der HIV-positiven Patienten kardiale Manifestationen auftreten. Zu den häufigsten HIV-assoziierten kardialen Manifestationen gehören der Perikarderguss und die chronisch aktive, fokale oder diffuse Myokarditis. Endokardiale Manifestationen bei HIV-positiven Patienten treten in Form der infektiösen Endokarditis und der nichtbakteriellen thrombotischen Endokarditis auf. In der Regel weisen HIV-assoziierte kardiale Manifestationen einen langsam progredienten Krankheitsverlauf auf. Komplikationen sind Folge eines langfristig unentdeckten Fortschreitens der Erkrankung, aber auch schnell progredienter Verlaufsformen. Aufgrund der Vielzahl HIV-assoziierter kardialer Manifestationen und deren möglicher Komplikationen ist daher neben der Früherkennung ein effektives diagnostisches und therapeutisches Vorgehen erforderlich. Seit Einführung der Proteaseinhibitoren in den 90er Jahren und der Anwendung der hochaktiven antiretroviralen Kombinationstherapie (HAART) konnten sowohl Mortalität als auch Morbidität der HIV-Infektion deutlich gesenkt werden. Die Auswirkungen der HAART auf das kardiovaskuläre System sind bisher nur in Ansätzen bekannt. Als Nebenwirkungen wurden metabolische Veränderungen in Form von Hyperlipoproteinämie und Insulinresistenz bei einer Vielzahl HIV-positiver Patienten beobachtet. Es kann davon ausgegangen werden, dass durch den Anstieg der kardiovaskulären Risikofaktoren unter der HAART in den nächsten Jahren eine erhöhte Rate kardialer Erkrankungen bei HIV-positiven Patienten auftreten wird. In dem vorliegenden Übersichtsartikel wird ein Überblick über die häufigsten kardialen Erkrankungen bei HIV-Infektionen gegeben. Zusätzlich werden Vorschläge zu Diagnostik und Therapie unterbreitet und eine Einschätzung über Veränderungen der HIV-assoziierten kardialen Manifestationen nach Einführung der HAART vorgenommen. Abstract. The human immunodeficiency virus (HIV) does not only affect the immune system. Other organs including the cardiovascular system are influenced by the HIV as well. Most common HIV-associated cardiac manifestations are pericardial effusion and chronic active, focal or diffuse myocarditis. In addition to peri- and myocardial disease, endocardiac manifestations occur as infective endocarditis and nonbacterial thrombotic endocarditis in HIV-infected patients. Although most of the cardiac manifestations associated with HIV-infection exhibit a slow progression, rapid courses may lead to fatal complications. Early screening of HIV-infected patients will identify the potentially fatal complications of HIV disease and permit efficient treatment. The use of highly active antiretroviral therapy (HAART) significantly reduced the mortality and morbidity of HIV-infected patients. However, the impact that HAART will have on the incidence and prevalence of cardiac complications in HIV-infected patients is still unknown. It can be predicted, that the long-term viral infection and the increase of cardiovascular risk factors by HAART will probably lead to an increased prevalence of HIV-infected individuals with cardiac complications in the next decade. The present review describes the most frequent HIV-associated cardiac manifestations including diagnostic and therapeutic perspectives. 相似文献
3.
Birgit T Priest Kenneth M Blumenthal Jaime J Smith Vivien A Warren McHardy M Smith 《Toxicon》2007,49(2):194-201
The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels. 相似文献
4.
Werner Benzer Marion Platter Neil B Oldridge Helmut Schwann Kurt Machreich Werner Kullich Karl Mayr Axel Philippi Alfred Gassner Jakob D?rler Stefan H?fer 《European journal of cardiovascular prevention and rehabilitation》2007,14(3):441-447
BACKGROUND: An objective of exercise-based cardiac rehabilitation is improvement in patient-reported outcomes such as health-related quality of life as well as anxiety and depressive symptoms. There are no direct comparisons of the effectiveness of inpatient and outpatient exercise-based cardiac rehabilitation programmes on patient-reported outcomes. METHODS: In this non-randomized study we collected patient-reported outcomes data with the MacNew Heart Disease health-related quality of life questionnaire and the Hospital Anxiety and Depression Scale at baseline, 1 month and again 3 months after admission to exercise-based cardiac rehabilitation in a cohort of 216 consecutive patients enrolled either in a 4-week inpatient exercise-based cardiac rehabilitation (n=62) or a 3-month outpatient exercise-based cardiac rehabilitation (n=87) and in a usual care group (n=67) to document the natural course in patient-reported outcome variables without exercise-based cardiac rehabilitation. RESULTS: Although MacNew health-related quality of life scores improved more with inpatient than outpatient exercise-based cardiac rehabilitation by month 1, the improvement was still significant in both groups at month 3 and also in the usual care group when compared to baseline. The health-related quality of life scores in the inpatient group, however, decreased between month 1 and 3 whereas they continued to improve in the outpatient group. The significant reduction in both anxiety and depressive symptoms in both exercise-based cardiac rehabilitation groups by month 1 was maintained at month 3 only with outpatient exercise-based cardiac rehabilitation. No significant changes over the 3 months were observed in the usual care group. CONCLUSION: Significant improvements of 1-month patient-reported outcomes are achieved in patients attending inpatient as well as outpatient exercise-based cardiac rehabilitation when compared with no exercise-based cardiac rehabilitation. In contrast to inpatient exercise-based cardiac rehabilitation, however, outpatient exercise-based cardiac rehabilitation leads to a further improvement of patient-reported outcomes. These results suggest that, if patients have to be admitted for inpatient exercise-based cardiac rehabilitation, this programme should be followed by an outpatient exercise-based cardiac rehabilitation to further improve and stabilize these patient-reported outcome variables. 相似文献
5.
6.
The determination of renal antigens in the urine with an immunoassay, based on monoclonal antibodies (moabs), is a noninvasive test system for the analysis and monitoring of renal injury. New moabs allowing an immunohistologic dissection of the human nephron were generated by a direct intrasplenic immunization of mice with pathologic urine samples. A sandwich enzyme immunoassay was developed to quantitate renal cell membrane antigens in the urine samples. A sandwich enzyme immunoassay was developed to quantitate renal cell membrane antigens in the urine. While antigen excretion in healthy individuals is low, preliminary data of a clinical investigation suggest the usefulness of these assay systems in diagnosis of tubular injury in human kidney transplant recipients. The immunoassay can provide very early hints of renal graft rejection prior to the appearance of clinical symptoms or the detection by routine clinical laboratory investigations. 相似文献
7.
8.
Birgit Herting MD Bettina Beuthien‐Baumann MD Katrin Pöttrich PhD Markus Donix MD Antje Triemer PhD Johannes B. Lampe MD Rüdiger von Kummer MD Karl Herholz MD Heinz Reichmann MD Vjera A. Holthoff MD 《Movement disorders》2007,22(4):490-497
Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction. 相似文献
9.
Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation? 总被引:5,自引:0,他引:5
Herwig Pokorny Michael Gnant Susanne Rasoul-Rockenschaub Bernd Gollackner Birgit Steiner Günter Steger Rudolf Steininger Ferdinand Mühlbacher 《American journal of transplantation》2005,5(4):788-794
The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m2 ) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m2 . Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA. 相似文献
10.
Claudia Trenkwalder MD Heike Benes MD Ludger Grote MD Svenja Happe MD Birgit Högl MD Johannes Mathis MD Gerda M. Saletu‐Zyhlarz MD Ralf Kohnen PhD CALDIR study group 《Movement disorders》2007,22(5):696-703
We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline. 相似文献