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51.
Cohen JH Faughnan ME Letarte M Vandezande K Kennedy SJ Krahn MD 《American journal of medical genetics. Part A》2005,137(2):153-160
Endoglin (ENG) and ALK-1 mutations cause hereditary hemorrhagic telangiecstasia (HHT), an autosomal dominant disorder leading to vascular dysplasia in the form of mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs). We proposed to compare two alternative strategies for management of HHT: screening HHT families with molecular diagnostic tests followed by targeted clinical screening versus conventional clinical screening. A decision analytic model was constructed to compare screening strategies for a hypothetical HHT family. The family consists of 1 index case and 13 relatives. The clinical screening protocol in use at the Canadian HHT Center in Toronto was assumed to be the standard of care. Unit costs for clinical screening (in Canadian dollars) were obtained from the 2003 Ontario Health Insurance Schedule of Benefits. Genetic screening costs were estimated for quantitative multiplex PCR and sequencing of Endoglin (ENG) and ALK-1 genes, as performed at HHT Solutions, Toronto. The genetic screening strategy resulted in a net cost of $4,060 per individual versus $5,975 for the clinical screening strategy. The genetic screening strategy would save $1,915 per family member or $26,810 saved per family. Sensitivity analyses revealed that the genetic screening strategy was cost saving over all plausible ranges of input variables for all hypothetical families tested. We concluded that a genetic screening strategy with targeted clinical screening is more economically attractive than conventional clinical screening and results in a reduction in the number of clinical tests for family members who do not have HHT. 相似文献
52.
Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and -sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy. 相似文献
53.
Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia 总被引:3,自引:0,他引:3
C Quigley C Cowell M Jimenez H Burger J Kirk M Bergin M Stevens J Simpson M Silink 《The New England journal of medicine》1989,321(3):143-151
To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early. 相似文献
54.
We investigated the saccade decision process by examining activity recorded in the frontal eye field (FEF) of monkeys performing 2 separate visual search experiments in which there were errors in saccade target choice. In the first experiment, the difficulty of a singleton search task was manipulated by varying the similarity between the target and distractors; errors were made more often when the distractors were similar to the target. On catch trials in which the target was absent the monkeys occasionally made false alarm errors by shifting gaze to one of the distractors. The second experiment was a popout color visual search task in which the target and distractor colors switched unpredictably across trials. Errors occurred most frequently on the first trial after the switch and less often on subsequent trials. In both experiments, FEF neurons selected the saccade goal on error trials, not the singleton target of the search array. Although saccades were made to the same stimulus locations, presaccadic activation and the magnitude of selection differed across trial conditions. The variation in presaccadic selective activity was accounted for by the variation in saccade probability across the stimulus-response conditions, but not by variations in saccade metrics. These results suggest that FEF serves as a saccade probability map derived from the combination of bottom-up and top-down influences. Peaks on this map represent the behavioral relevance of each item in the visual field rather than just reflecting saccade preparation. This map in FEF may correspond to the theoretical salience map of many models of attention and saccade target selection. 相似文献
55.
The airway epithelium is the first cellular component of the lung to be encountered by the particles and pathogens present in inhaled air. In addition to its role as a physical barrier, the immunological activity of the airway epithelium is an essential part of the pulmonary immune system. This means that the symptoms of lung diseases that involve immunological mechanisms are frequently exacerbated by infection of the airway epithelium with respiratory viruses. The virus-induced enhancement of immunological activity in infected epithelial cells is well characterized. However, the effects that contaminants of inhaled air have upon the infectivity and replication of respiratory viruses and the inflammation they cause, are comparatively unknown. In this study, we have shown that pre-exposure of airway epithelial cells to bacterial lipopolysaccharides or a proteolytically active house dust mite allergen, is able to, respectively, inhibit or enhance the level of cellular infection with respiratory syncytial virus and similarly alter virus-induced expression of the inflammatory chemokine interleukin-8. These results suggest that respiratory syncytial virus infection and the inflammation caused by respiratory syncytial virus may be modified by the biologically active contaminants of indoor air. 相似文献
56.
57.
58.
Devasia RA Varma JK Whichard J Gettner S Cronquist AB Hurd S Segler S Smith K Hoefer D Shiferaw B Angulo FJ Jones TF 《Microbial drug resistance (Larchmont, N.Y.)》2005,11(4):371-377
Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes. 相似文献
59.
D McCormick I Wallace J Kirk S Dinsmore I Allen 《British journal of experimental pathology》1983,64(1):103-115
A permanent cell line has been established from a human intracranial secondary melanoma. During 3 years of continuous growth in vitro the cells have maintained their characteristic phenotypic properties including melanin production. The cultured cells are highly tumorigenic in the athymic mouse and the tumours produced are histologically identical to the human tumour of origin. 相似文献
60.
Face processing differences have been observed between AS and control subjects at the behavioural and neurological levels. The purpose of the present study was to investigate the neurophysiological basis of processing faces and facial features (eyes and mouths) in adults with AS relative to age- and gender-matched typically-developing controls. These results were compared with ERPs generated to objects in both groups to determine if any differences were specific to facial stimuli. Although both groups elicited earlier N170 latencies to faces than to face parts and to eyes relative to mouths, adults with AS exhibited delayed N170 latencies to faces and face parts relative to controls. This difference was not observed to objects. Together these findings suggest that adults with AS may be slower to process facial information. 相似文献