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91.
Treatment of End-Stage Renal Disease in Central and Eastern Europe: Overview of Current Status and Future Needs 总被引:2,自引:0,他引:2
Bolesaw Rutkowski Aleksandru Ciocalteu Ljubica Djukanovic Istvan Kiss Aleksander Kovac Momir Polenakovic Zvonimir Puretic Rafail Rozental Maria Stanaityte Irina Tareyeva Vladimir Teplan Jeff Zavitz Krivoshiev Stefan & Kveder Rado 《Artificial organs》1998,22(3):187-191
The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990–1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RTT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries. 相似文献
92.
Al-Sarraj S King A Troakes C Smith B Maekawa S Bodi I Rogelj B Al-Chalabi A Hortobágyi T Shaw CE 《Acta neuropathologica》2011,122(6):691-702
Neuronal cytoplasmic inclusions (NCIs) containing phosphorylated TDP-43 (p-TDP-43) are the pathological hallmarks of motor
neuron disease/amyotrophic lateral sclerosis (MND/ALS) and FTLD-TDP. The vast majority of NCIs in the brain and spinal cord
also label for ubiquitin and p62, however, we have previously reported a subset of TDP-43 proteinopathy patients who have
unusual and abundant p62 positive, TDP-43 negative inclusions in the cerebellum and hippocampus. Here we sought to determine
whether these cases carry the hexanucleotide repeat expansion in C9orf72. Repeat primer PCR was performed in 36 MND/ALS, FTLD-MND/ALS and FTLD-TDP cases and four controls. Fourteen individuals with
the repeat expansion were detected. In all the 14 expansion mutation cases there were abundant globular and star-shaped p62
positive NCIs in the pyramidal cell layer of the hippocampus, the vast majority of which were p-TDP-43 negative. p62 positive
NCIs were also abundant in the cerebellar granular and molecular layers in all cases and in Purkinje cells in 12/14 cases
but they were only positive for p-TDP-43 in the granular layer of one case. Abundant p62 positive, p-TDP-43 negative neuronal
intranuclear inclusions (NIIs) were seen in 12/14 cases in the pyramidal cell layer of the hippocampus and in 6/14 cases in
the cerebellar granular layer. This unusual combination of inclusions appears pathognomonic for C9orf72 repeat expansion positive MND/ALS and FTLD-TDP which we believe form a pathologically distinct subset of TDP-43 proteinopathies.
Our results suggest that proteins other than TDP-43 are binding p62 and aggregating in response to the mutation which may
play a mechanistic role in neurodegeneration. 相似文献
93.
Role of endogenous cannabinoids in synaptic signaling 总被引:32,自引:0,他引:32
Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns. 相似文献
94.
95.
96.
Kindling-induced epilepsy alters calcium currents in granule cells of rat hippocampal slices 总被引:2,自引:0,他引:2
Istvan Mody James N. Reynolds Michael W. Salter Peter L. Carlen John F. MacDonald 《Brain research》1990,531(1-2):88-94
Single electrode voltage-clamp recordings were obtained from dentate gyrus granule cells (GCs) in hippocampal slices of control and commissurally kindled rats. Two types of calcium currents, a transient and a sustained current, were studied in control and kindled neurons. The threshold of the transient calcium current was lowered in kindled GCs. The sustained calcium current was absent in kindled neurons but it could be restored by the intracellular administration of the calcium chelator EGTA. Our findings are consistent with the hypothesis that the loss of an intraneuronal calcium binding protein (Calbindin-D28K; CaBP) reduces the intraneuronal calcium buffering capacity in kindled neurons and results in the enhanced calcium-dependent inactivation of sustained calcium currents. 相似文献
97.
Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific. 总被引:2,自引:0,他引:2
Thyroid hormone affects the contractile and electrophysiological properties of the cardiac myocyte that result in part from changes in the expression of thyroid hormone-responsive cardiac genes, including those that regulate membrane ion currents. To determine the molecular mechanisms underlying this effect, expression of a voltage-gated K+ channel, Kv1.5, was measured in response to thyroid hormone. Using quantitative RT-PCR methodology, the content of Kv1.5 messenger RNA (mRNA) in left ventricles of euthyroid rats was 4.25+/-0.6x10(-20) mol/microg total RNA and was decreased by 70% in the hypothyroid rat ventricle to 1.27+/-0.80x10(-20) mol/microg RNA (P<0.01). Administration of T3 to hypothyroid animals restored ventricular Kv1.5 mRNA to control levels within 1 h of treatment, making this the most rapid T3-responsive cardiac gene reported to date. The half-life of Kv1.5 mRNA was 1.9 h and 2.0 h in euthyroid and hypothyroid ventricles, respectively, and T3 treatment of the rats did not alter its half-life. In atrial myocardium, expression of Kv1.5 mRNA (6.10+/-0.37x10(-20) mol/microg RNA) was unaltered by thyroid hormone status. The myocyte-specific and chamber-selective expression of Kv1.5 mRNA was confirmed in primary cultures of rat atrial and ventricular myocytes. 相似文献
98.
Dr Prof Bernard Escudier MD Prof Anna Pluzanska MD Piotr Koralewski MD Prof Alain Ravaud MD Prof Sergio Bracarda MD Prof Cezary Szczylik MD Christine Chevreau MD Marek Filipek MD Bohuslav Melichar MD Prof Emilio Bajetta MD Prof Vera Gorbunova MD Jacques-Olivier Bay MD Istvan Bodrogi MD Agnieszka Jagiello-Gruszfeld MD Nicola Moore MSc for the AVOREN Trial investigators 《Lancet》2008,370(9605):2103-2111
99.
100.
Timing of therapeutic intervention determines functional and survival outcomes in a mouse model of late infantile batten disease. 总被引:1,自引:0,他引:1
Mario A Cabrera-Salazar Eric M Roskelley Jie Bu Bradley L Hodges Nelson Yew James C Dodge Lamya S Shihabuddin Istvan Sohar David E Sleat Ronald K Scheule Beverly L Davidson Seng H Cheng Peter Lobel Marco A Passini 《Molecular therapy》2007,15(10):1782-1788
Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a monogenic disorder caused by the loss of tripeptidyl peptidase 1 (TPP1) activity as a result of mutations in CLN2. Absence of TPP1 results in lysosomal storage with an accompanying axonal degeneration throughout the central nervous system (CNS), which leads to progressive neurodegeneration and early death. In this study, we compared the efficacies of pre- and post-symptomatic injections of recombinant adeno-associated virus (AAV) for treating the cellular and functional abnormalities of CLN2 mutant mice. Intracranial injection of AAV1-hCLN2 resulted in widespread human TPP1 (hTPP1) activity in the brain that was 10-100-fold above wild-type levels. Injections before disease onset prevented storage and spared neurons from axonal degeneration, reflected by the preservation of motor function. Furthermore, the majority of CLN2 mutant mice treated pre-symptomatically lived for at least 330 days, compared with a median survival of 151 days in untreated CLN2 mutant controls. In contrast, although injection after disease onset ameliorated lysosomal storage, there was evidence of axonal degeneration, motor function showed limited recovery, and the animals had a median lifespan of 216 days. These data illustrate the importance of early intervention for enhanced therapeutic benefit, which may provide guidance in designing novel treatment strategies for cLINCL patients. 相似文献