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71.
Age-related progression of tau pathology in brains of baboons 总被引:3,自引:0,他引:3
Recently, cytoskeletal changes associated with abnormally phosphorylated tau protein were demonstrated in neurons and glial cells of two aged baboons (Papio). The present study examines the effects of age on the development of tau pathology in baboons. Brains of 50 baboons ranging in age from 1 to 30 years were categorized into four age groups: Group I: 1–10 years [n = 9], group II: 11–20 years [n = 13], group III: 21–25 years [n = 17], group IV: 26–30 years [n = 11]). Whole hemisphere sections (100 μm) were examined using phosphorylation-dependent anti-tau antibodies. Cytoskeletal changes were completely absent in animals of group I. In group II four animals (31%) exhibited cytoskeletal changes which were rated as mild or moderate. In group III abnormal tau was found in 12 brains (71%) ranging in severity from mild to severe. Finally, in group IV 10 out of 11 animals (91%) exhibited some degree of tau pathology which was rated as severe in 4 animals (36%). A statistically significant relationship was found between advancing age and progression of tau pathology in baboons. In conclusion, the present findings underline the value of the baboon as a potential nonhuman primate model for age-related tau pathology afflicting the human brain. 相似文献
72.
Frederick Gregory D.; Amirkhan Robin H.; Schultz Roger A.; Friedberg Errol C. 《Human molecular genetics》1994,3(10):1783-1788
Individuals affected by the autosomal recessive disease xerodermapigmentosum (XP) are acutely sensitive to sunlight and predisposedto skin cancer on exposed areas. Cells cultured from XP patientsare both UV sensitive and defective in the nucleotide excisionrepair of damaged DNA. These cellular phenotypes are amenableto experimental strategies employing complementation, an approachpreviously used to demonstrate the correction of XP-D phenotypesfollowing the introduction of the XPD (ERCC2) gene. In the presentstudy, we have characterized the genomic organization of theXPD (ERCC2) gene and found it to be comprised of 23 exons. Thesedata were helpful in evaluating the functional integrity ofalleles in two XP-D cell lines. In cell line GM436 a C 相似文献
73.
D. H. Schultz V. L. Shah W. Shay P. Wang 《Medical & biological engineering & computing》1977,15(2):98-105
The numerical solutions of diffusion equations have been obtained for the cases of oxygen and carbon dioxide diffusing through blood flowing between two porous parallel planes. It is assumed that at the entrance to the channel the concentration profiles are uniform and the velocity profile is fully developed. The rheological characteristics of blood are described by the Casson equation. The computations have been made employing the explicit finite-difference forward-marching procedure. The results have been obtained for a wide range of yield numbers, inlet partial pressures, pH, membrane resistances and haemoglobin concentrations. 相似文献
74.
Alberto L. Dubrovsky A. L. Taratuto G. Sevlever M. Schultz E. Pegoraro R. C. Hoop E. P. Hoffman 《American journal of medical genetics. Part A》1995,55(3):342-348
We report on the first patient identified with myotonic dystrophy and Duchenne muscular dystrophy (DMD). The family of the propositus had a strong history of myotonic dystrophy, and there was an intrafamilial pathological expansion of the responsible CTG repeat between the mildly affected mother (160 repeats; normal 27 repeats) and her more severely affected son (650 repeats), and his sister (650 repeats). The propositus was an isolated case of Duchenne muscular dystrophy with marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory post age 16. Myotonic dystrophy could interfere to some extent with the progression of Duchenne dystrophy. However, other interpretations are possible. Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry could be sufficient to ameliorate typical DMD clinical severity, or the patient may present a somatic mosaic. The pathophysiological interactions of these two unlinked disorders are discussed at the clinical and histopathological levels. © 1995 Wiley-Liss, Inc. 相似文献
75.
Harvey M.B.; Leco K.J.; Arcellana-Panlilio M.Y.; Zhang X.; Edwards D.R.; Schultz G.A. 《Human reproduction (Oxford, England)》1995,10(3):712-718
Several growth factor ligand and receptor gene products havebeen shown to play roles during preimplantation mammalian development.Genes for insulin-like growth factors (IGFs), transforming growthfactors (TGFs), fibroblast growth factor (FGF), platelet-derivedgrowth factor (PDGF) and receptors for insulin, IGF, PDGF, TGFand epidermal growth factor (EGF) are expressed by early embryosof several species including mouse, rat, cow and sheep. Rolesof growth factors during early development have been demonstratedby addition of purified growth factors to culture medium orby molecular genetic techniques that interfere with gene expression.In this way, it has been shown that successful development ofthe blastocyst is dependent on the action of epidermal growthfactor (EGF) and leukaemia inhibitory factor (LIF). Recent experimentsshow that both LIF and EGF stimulate secretion of urokinase-typeplasminogen activator (uPA) and gelatinase B/ matrix metalloproteinase-9(MMP-9) in day 7 mouse blastocyst outgrowths. At the same time,tissue inhibitors of MMPs (TIMPs) are also expressed by embryonic,decidual and uterine tissues during the implantation process.It appears that LIF may act directly or indirectly, by inducingthe expression of other cytokines, to regulate the temporaland spatial production and activity of proteases and proteaseinhibitors to create a favourable environment for implantation. 相似文献
76.
James L M Ferrara Claudio Anasetti Edward Stadtmauer Joseph Antin John Wingard Stephanie Lee John Levine Kirk Schultz Frederick Appelbaum Robert Negrin Sergio Giralt Christopher Bredeson Helen Heslop Mary Horowitz 《Biology of blood and marrow transplantation》2007,13(11):1268-1285
Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years. 相似文献
77.
Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions 总被引:8,自引:0,他引:8
1. This study investigates the behavioral conditions in which dopamine (DA) neurons of substantia nigra and adjoining areas A8 and A10 respond with impulses to visual and auditory trigger stimuli eliciting immediate arm- and eye-movement reactions. 2. In a formal task, the rapid opening of the door of a small, food-containing box located at eye level ahead of the animal served as visible and audible trigger stimulus. Most DA neurons on the contralateral side responded to this stimulus with a short burst of impulses with median onset latency of 50 ms and duration of 90 ms (75% of 164 neurons). Similar responses were seen in a comparable fraction of DA neurons during ipsilateral task performance, suggesting that responses were not specific for the limb being used. 3. When the sensory components of the door opening stimulus were separated, DA neurons typically responded in a similar manner to the moving visual stimulus of the opening door, the low-intensity sliding noise of the opening door, and the 1-kHz sound of 90-92 dB intensity emitted from a distant source at the onset of door opening. Responses to each component alone were lower in magnitude than to all three together. 4. In a variation of the task, a neighboring, identical food box opened in random alternation with the other box but without permitting animals to reach out (asymmetric, direct-reaction go/no-go task). With each sensory component, DA neurons typically responded both to opening of go and no-go boxes. Responses were enhanced when stimuli elicited limb movements in go trials. 5. Monkeys reacted to door opening with target-directed saccadic eye movements in the majority of both go and no-go trials. Neuronal responses were equally present during the occasional absence of eye movements. Thus responses were not specific for the initiation of individual arm or eye movements. 6. Neuronal responses were absent when the same stimuli occurred outside of the behavioral task with target-direct arm and eye movements lacking. This shows that responses were not of purely sensory nature but were related to the capacity of the stimulus for eliciting behavioral reactions. 7. In a variation of the go/no-go task, an instruction light illuminated 2-3 s before door opening prepared the animal to perform the reaching movement on door opening or to refrain from moving (asymmetric, instruction-dependent go/no-go task).(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
78.
The actions of prolonged treatment of rats within imipramine or lithium chloride on the β-adrenergic cAMP generating system of the cerebellum were compared in normal animals and in rats degranulated by neonatal X-irradiation. Whereas in normal animals imipramine treatment is without significant effect on the cerebellar cAMP system but lowers the β-adrenoceptor density significantly, in degranulated animals the cAMP system becomes subsensitive towards norepinephrine after prolonged imipramine treatment. These data support the hypothesis that in the cerebellum imipramine acts predominantly on β-adrenoceptors located particularly on Purkinje cells. Prolonged lithium treatment exhibited no significant effects on β-receptors nor the noradrenergic cAMP generating system of normal and degranulated cerebella. 相似文献
79.
Janice S. Lee Carol W. Bassim Harvey Kushner Ann G. Carr Pamela J. Gardner Laura A. Harney Kris Ann P. Schultz Douglas R. Stewart 《American journal of medical genetics. Part A》2019,179(9):1820-1825
Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor‐predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1‐carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite‐wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi‐square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1‐associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation. 相似文献
80.
A de novo X;3 translocation in Rett syndrome 总被引:6,自引:0,他引:6
H Y Zoghbi D H Ledbetter R Schultz A K Percy D G Glaze 《American journal of medical genetics》1990,35(1):148-151
Rett syndrome is a neurodegenerative disorder that occurs exclusively in females. The syndrome is sporadic in most cases with the exception of a few familial cases with an inheritance pattern through maternal lines. These observations raised the possibility that Rett syndrome may be due to an X-linked dominant mutation which is lethal in the male. To evaluate this hypothesis, we have systematically performed high-resolution chromosome analysis on 28 patients with Rett syndrome searching for deletions and/or translocations. In one patient, a de novo balanced translocation was observed with the chromosome constitution of 46,X,t(X;3) (p22.11;q13.31). This finding supports the hypothesis of an X-linked dominant mutation and suggests that the Rett gene might map to distal Xp21 or proximal Xp22. 相似文献