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Thomas J. Cahill Shehan Hettiaratchy Alex Clarke Peter E.M. Butler 《Transplantation reviews (Orlando, Fla.)》2006,20(2):76-81
Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant procedures are well established, it is possible to assess the predictive value and limitations of animal models. These results are of great importance in the current debate about composite tissue allotransplantation (CTA) and in particular facial transplantation. This progression of CTA from animal models to man is outlined and compared with early renal, cardiac, and liver transplants. There is some evidence to suggest that animal models may have been misleading in CTA and that this has effectively delayed the transition to humans. The role for animal models in facial transplantation, which is currently making the step to clinical trials, is discussed. 相似文献
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Kelly Garrett Allison Butler Wayne R Cohen 《The journal of maternal-fetal & neonatal medicine》2005,17(1):49-53
OBJECTIVE: To characterize dysfunctional labors that lead to cesarean delivery in the second stage and to assess the accuracy of diagnoses of abnormal fetal descent. METHODS: Thirty-one patients delivered by cesarean during the second stage because of abnormal labor or presumed cephalopelvic disproportion were studied and compared to 62 control cesarean cases delivered for the same indications in the first stage. The clinical diagnosis of dysfunctional labor that led to the cesarean was compared to the diagnosis made by retrospective analysis of the labor curves. RESULTS: Cases did not differ from controls delivered in the first stage in maternal age, race, parity, gestational age, weight gain, or the frequency of associated medical complications. The newborns were not significantly different in birth weight,ponderal index, sex, or the incidence of low Apgar scores. Among study patients, 94% had a second stage labor dysfunction determined by graphic labor analysis, predominantly arrest of descent (69%) and failure of descent (28%). In 79% of cases a dysfunctional first stage preceded the abnormal second stage. Among these first stage labor abnormalities, 68% were not recognized during the labor. CONCLUSION: Characteristics of patients delivered by cesarean during the second stage were similar to those delivered before full cervical dilatation. Second stage labor abnormalities were usually preceded by an abnormal first stage. There was considerable inaccuracy in the diagnosis of second stage labor dysfunction. 相似文献
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Apparent inactivation of alpha 1-antiproteinase by sulphur-containing radicals derived from penicillamine 总被引:2,自引:0,他引:2
alpha 1-Antiproteinase is the major inhibitor of proteolytic enzymes, such as elastase, in human plasma. Its elastase-inhibitory capacity can be inactivated by exposure to hydroxyl radicals (.OH) generated either by pulse radiolysis or by an Fe3+-EDTA/H2O2/ascorbic acid system. Inactivation of alpha 1-antiproteinase by radiolytically-generated .OH under anoxic conditions was decreased by adding a range of anti-inflammatory drugs to the reaction mixtures, including the thiol compound penicillamine. However, under conditions favouring formation of oxysulphur radicals, protection by thiols such as penicillamine was much decreased. It is proposed that sulphur-containing radicals resulting from attack of biologically-produced oxidants upon penicillamine in the presence of O2 can themselves inactivate alpha 1-antiproteinase, and that such radicals might contribute to the side-effects produced by penicillamine or gold thiol therapy in rheumatoid arthritis. 相似文献
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Ahmed Ali Sirkku Niissalo Jarkko Hietanen Mikael Laine Riina Rautemaa Yrjö Konttinen 《Journal of oral pathology & medicine》2005,34(6):347-351
BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic opportunistic candida infection. We clarified the presence, localization and participation of alpha-defensin-1 in host response against chronic candidal stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria and in the epithelium, in part in intraepithelial microabscesses. Staining intensity of individual neutrophils varied and was associated with peri- and extracellular staining, in particular in the superficial epithelial cell layers. In controls only very few homogeneously staining neutrophils were detected intravascularly without any extracellular alpha-defensin-1 deposition. CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation and release of alpha-defensin-1 to peri- and extracellular matrix. This together with the epithelial cell migration from the basal layer to epithelial surface leads to alpha-defensin-1 rich protective shield in the most superficial epithelial cell layers. 相似文献
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Ian F. Dunn Pankaj K. Agarwalla Alexander M. Papanastassiou William E. Butler Edward R. Smith 《Child's nervous system》2007,23(10):1191-1194
Objective Approximately 10% of patients with neurofibromatosis I (NFI) patients will have central nervous system (CNS) tumors. The most
common of these are hypothalamic–optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. While isolated
pilocytic astrocytomas in NFI are well described, the appearance of multiple pilocytic astrocytomas in an individual patient
is less common. The most frequent combination in NFI patients with more than one pilocytic astrocytoma is optic tract/hypothalamic
and brainstem. Other combinations are exceedingly rare; multiple pilocytic astrocytomas have only been reported once in the
cerebral hemispheres in a patient with NFI. This report presents the first documented case, to our knowledge, of multiple
pilocytic astrocytomas in the cerebellum of a patient with NF1.
Methods Case report.
Conclusion The finding of multiple cerebellar pilocytic astrocytomas in a patient with NF1 is important because it expands the spectrum
of presentations for patients with NF1 and also highlights specific diagnostic and therapeutic challenges faced by the treating
physicians. The genetic and molecular basis of NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant
to both patients with NF1 and all patients with multiple posterior fossa tumors. 相似文献
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Jere Paavola Matti Viitasalo P?ivi J Laitinen-Forsblom Michael Pasternack Heikki Swan Ilkka Tikkanen Lauri Toivonen Kimmo Kontula Mika Laine 《European heart journal》2007,28(9):1135-1142
AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT. 相似文献