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71.
Nevzorova YA Bangen JM Hu W Haas U Weiskirchen R Gassler N Huss S Tacke F Sicinski P Trautwein C Liedtke C 《Hepatology (Baltimore, Md.)》2012,56(3):1140-1149
Liver fibrogenesis is associated with the transition of quiescent hepatocytes and hepatic stellate cells (HSCs) into the cell cycle. Exit from quiescence is controlled by E-type cyclins (cyclin E1 [CcnE1] and cyclin E2 [CcnE2]). Thus, the aim of the current study was to investigate the contribution of E-type cyclins for liver fibrosis in man and mice. Expression of CcnE1, but not of its homolog, CcnE2, was induced in fibrotic and cirrhotic livers from human patients with different etiologies and in murine wild-type (WT) livers after periodical administration of the profibrotic toxin, CCl(4) . To further evaluate the potential function of E-type cyclins for liver fibrogenesis, we repetitively treated constitutive CcnE1(-/-) and CcnE2(-/-) knock-out mice with CCl(4) to induce liver fibrosis. Interestingly, CcnE1(-/-) mice were protected against CCl(4) -mediated liver fibrogenesis, as evidenced by reduced collagen type I α1 expression and the lack of septum formation. In contrast, CcnE2(-/-) mice showed accelerated fibrogenesis after CCl(4) treatment. We isolated primary HSCs from WT, CcnE1(-/-) , and CcnE2(-/-) mice and analyzed their activation, proliferation, and survival in vitro. CcnE1 expression in WT HSCs was maximal when they started to proliferate, but decreased after the cells transdifferentiated into myofibroblasts. CcnE1(-/-) HSCs showed dramatically impaired survival, cell-cycle arrest, and strongly reduced expression of alpha smooth muscle actin, indicating deficient HSC activation. In contrast, CcnE2-deficient HSCs expressed an elevated level of CcnE1 and showed enhanced cell-cycle activity and proliferation, compared to WT cells. Conclusions: CcnE1 and CcnE2 have antagonistic roles in liver fibrosis. CcnE1 is indispensable for the activation, proliferation, and survival of HSCs and thus promotes the synthesis of extracellular matrix and liver fibrogenesis. (HEPATOLOGY 2012;56:1140-1149). 相似文献
72.
Sebastian J. Buss Mostafa Emami Derliz Mereles Grigorios Korosoglou Arnt V. Kristen Andreas Voss Dieter Schellberg Christian Zugck Christian Galuschky Evangelos Giannitsis Ute Hegenbart Anthony D. Ho Hugo A. Katus Stefan O. Schonland Stefan E. Hardt 《Journal of the American College of Cardiology》2012
73.
Ute Strehl Boris Kotchoubey Simone Martinetz Niels Birbaumer 《Journal of neurotherapy》2013,17(3):200-213
In patients with epilepsy, not only seizures but also cognitive, emotional, and social functioning are of increasing interest in research (Kelley, Jacobs, &; Lowenstein, 2009). As a decrease in cognitive functions over the course of the illness is usually reported, we wanted to explore changes in Intelligence Scores observed after a neurofeedback treatment in patients with drug-resistant epilepsies. In a controlled study that compared the outcome of three different interventions (training to regulate slow cortical potentials, N = 34; training to regulate breath rate and the amount of carbon dioxide in the end tidal volume of the exhaled air, N = 11; modification of drug regime, N = 25), pre- and postmeasurements of a short version of the Wechsler Intelligence Scale were applied. The interval between the two assessments was more than 12 months, with a mean of 61 weeks. Mean age of the patients was 35, with a range from 17 to 57. The highly significant 7-point increment of IQ only after training of slow cortical potentials was not related to clinical (e.g., seizure reduction) or neuropsychological (e.g., attention and memory) variables. Instead, it was related to psychophysiological measures: IQ change was inversely related to the Latency of the P300 component of event-related brain potentials and directly related to the Latency of the P2 component and the increase of N2 Amplitude during training. We conclude that regulation training of slow cortical potentials improves IQ in patients with refractory partial epilepsy, which might be related to an improved ability for controlled allocation of cognitive resources. 相似文献
74.
Tobias Geis Klaus Marquard Tanja Rödl Christof Reihle Sophie Schirmer Thekla von Kalle Antje Bornemann Ute Hehr Markus Blankenburg 《Neurogenetics》2013,14(3-4):205-213
Defects in dystroglycan post-translational modification result in congenital muscular dystrophy with or without additional eye and brain involvement, are referred to as secondary dystroglycanopathies and have been associated with mutations in 11 different genes encoding glycosyltransferases or associated proteins. However, only one patient with a mutation in the dystroglycan encoding gene DAG1 itself has been described before. We here report a homozygous novel DAG1 missense mutation c.2006G>T predicted to result in the amino acid substitution p.Cys669Phe in the β-subunit of dystroglycan in two Libyan siblings. The affected girls presented with a severe muscle–eye–brain disease-like phenotype with distinct additional findings of macrocephaly and extended bilateral multicystic white matter disease, overlapping with the cerebral findings in patients with megalencephalic leucoencephalopathy with subcortical cysts. This novel clinical phenotype observed in our patients further expands the clinical spectrum of dystroglycanopathies and suggests a role of DAG1 not only for dystroglycanopathies but also for some forms of more extensive and multicystic leucodystrophy. 相似文献
75.
76.
Johanna Christina Czeschik Ute Hehr Britta Hartmann Hermann-Josef Lüdecke Thorsten Rosenbaum Bernd Schweiger Dagmar Wieczorek 《European journal of medical genetics》2013,56(12):689-694
Walker–Warburg syndrome (WWS) is a severe muscular dystrophy with eye and brain malformations. On a molecular level, WWS is a disorder of the O-linked glycosylation of α-dystroglycan and therefore referred to as one of the dystroglycanopathies. The disease family of muscular dystrophy–dystroglycanopathy (MDDG) contains a spectrum of severe to mild disorders, designated as MDDG type A to C. WWS, as the most severe manifestation, corresponds to MDDG type A. Defects in the genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GTDC2, G3GALNT2, GMPPB, B3GNT1, TMEM5 and COL4A1 and ISPD have been described as causal for several types of MDDG including WWS, but can only be confirmed in about 60–70% of the clinically diagnosed individuals. The proteins encoded by these genes are involved in the posttranslational modification of α-dystroglycan. Mutations in POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GMPPB, TMEM5 and COL4A1 and ISPD lead to a wide spectrum of phenotypes of congenital muscular dystrophies with or without eye and brain abnormalities. Patients with WWS frequently demonstrate a complete lack of psychomotor development, severe eye malformations, cobblestone lissencephaly and a hypoplastic cerebellum and brainstem, seizures, hydrocephalus and poor prognosis. Here, we present a boy with WWS who showed compound heterozygous changes in ISPD and discuss the clinical and radiological phenotype and the molecular genetic findings, including a novel pathogenic mutation in ISPD. 相似文献
77.
78.
Eugen Sandica Ute Blanz Lotfi Ben Mime Ursula Schultz‐Kaizler Deniz Kececioglu Nikolaus Haas Guenther Kirchner Edzard zu Knyphausen Volker Lauenroth Michiel Morshuis 《Artificial organs》2016,40(3):225-232
This retrospective study reviews our results regarding the long‐term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2–16.5], median weight 13 kg [IQR 4.2–67.2]). Twenty‐two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single‐ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2–17.9), and the median weight was 54.9 kg (IQR 27.7–66). In the Berlin Heart group, the median support time was 65 days (IQR 4–619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1–1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long‐term mechanical circulatory support in patients with two‐ and single‐ventricle physiology with a low rate of adverse events. 相似文献
79.
Katrin Schaller Ute Mons 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2018,61(11):1429-1438
In Germany, several tobacco control policies have been implemented since 2002. These include tobacco tax increases, restrictions on sale and advertising, smoke-free legislation, and health warnings on tobacco products. All of those contributed to the emerging trend towards nonsmoking – especially among youth and young adults – as well as to the impressive decline of cigarette sales from 145.1 billion cigarettes in 2002 to 75.8 billion in 2017. Despite this, still 13% of all deaths are attributable to smoking in Germany.Other countries are acting in a more committed manner and are implementing much stronger tobacco control policies than Germany. Germany is the only EU country that doesn’t yet have a billboard ban on tobacco advertising, the smoke-free legislation is weak due to exceptions, and for more than ten years the tobacco tax has not been markedly increased. Globally, more than 30 countries have implemented at the highest possible level four of the six most important tobacco control policies as defined by the World Health Organization – Germany has implemented only two policies. Therefore, on an international scale, Germany is clearly lagging behind in tobacco control and on the European Tobacco Control Scale it is ranked second last. A more committed and compelling approach towards tobacco control is required in Germany to reach a position in terms of protecting the population from the devastating health hazards of smoking, which would be appropriate for a leading industrial nation. 相似文献
80.
Die Unfallchirurgie - Densfrakturen zählen zu den häufigsten Verletzungen der Wirbelsäule. Neben den klassischen Verfahren kann die dorsale C1-C2-Fusion nach Goel-Harms als... 相似文献