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Marsh JC; Will AJ; Hows JM; Sartori P; Darbyshire PJ; Williamson PJ; Oscier DG; Dexter TM; Testa NG 《Blood》1992,79(12):3138-3144
We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. 相似文献
73.
Z Farid N I Girgis M Kamal E Bishay M E Kilpatrick 《Scandinavian journal of infectious diseases》1990,22(4):505-506
Aztreonam treatment was successful in 4 cases of typhoid fever. The patients were seriously ill with growth of Salmonella typhi in blood cultures despite treatment with chloramphenicol. Aztreonam appears to be a useful alternative to standard therapy of typhoid fever. 相似文献
74.
Dexras1 is a novel GTP-binding protein that shares structural similarity with the Ras family of small molecular weight GTPases and is strongly and rapidly induced during treatment with dexamethasone. The function of Dexras1 and its contribution to glucocorticoid-dependent signaling in the corticotroph cell are unknown. The present study was undertaken to examine the potential role of Dexras1 in the regulation of peptide hormone secretion in the AtT-20 corticotroph cell line. To determine the effects of Dexras1 expressed independently of glucocorticoid treatment, expression plasmids for wild-type and constitutively active mutant Dexras1 proteins were cotransfected with human GH (hGH), which provides an ectopic marker for the stimulus-coupled secretory pathway. GTP binding properties and the GTP to GDP ratio of wild-type and mutant Dexras1 proteins were examined in transiently transfected AtT-20 and COS-7 cells. Stimulated and constitutive components of secretion were assessed after 2-h incubations with 5 mM 8-Br-cAMP or control. cAMP treatment led to a 2-fold increase in hGH secretion relative to control. Cotransfection of wild-type Dexras1 had no effect on cAMP-stimulated hGH secretion, but a constitutively active mutant, Dexras[A178V], attenuated stimulated secretion by 86% (P < 0.01). A double-mutant containing a deletion of the carboxyl terminus isoprenylation site, Dexras[A178V/C277term], did not inhibit cAMP-stimulated hGH secretion, indicating that the effect is prenylation dependent. These findings suggest that activation of Dexras1 has important functional consequences leading to inhibition of stimulus-secretion coupling in corticotroph cells. Because Dexras1 messenger RNA is strongly and rapidly induced during glucocorticoid treatment, these results raise the possibility that Dexras1 may participate in the signal transduction pathways that govern the rapid regulatory effects of glucocorticoids on peptide hormone secretion in corticotroph cells. 相似文献
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Kathleen T. Brady Lorraine R. Dustan Dorothy E. Grice Bonnie S. Danksy Dean Kilpatrick 《The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions》1995,4(4):306-312
The authors explored the relationship between assault, substance use disorders, and personality disorders by interviewing 82 substance-dependent inpatients with a structured interview concerning physical and sexual assault as well as the Structured Clinical Interview for DSM-III-R, parts I and II. Sixty percent of subjects met criteria for a personality disorder. Individuals who had experienced assault (n = 43) were more likely to have all types of personality disorder diagnoses (P ≤ 0.001). Those who reported childhood assault were more likely to have Cluster B personality disorders and to meet criteria for more than two personality disorder diagnoses (P ≤ 0.05) compared with those who reported adult assault only. Personality disorders were commonly diagnosed in this group of treatment-seeking, substance-dependent individuals. The effect of substance abuse as well as assault on the development and presentation of personality disorders is likely to be substantial. 相似文献
77.
Namjou B Nath SK Kilpatrick J Kelly JA Reid J James JA Harley JB 《Arthritis and rheumatism》2002,46(11):2937-2945
OBJECTIVE: Arthritis is a common manifestation in systemic lupus erythematosus (SLE), appearing in approximately 85% of patients. Often, the polyarthritis at presentation of SLE cannot be distinguished from rheumatoid arthritis (RA) by physical examination or history. Indeed, physicians initially tell many SLE patients that they have RA (one source of "self-reported RA"), only to have SLE established later. In addition, RA aggregates in families with an SLE proband. We predicted that pedigrees multiplex for both SLE and for self-reported RA would better isolate particular genetic effects. If this proved to be true, we would then use the increased genetic homogeneity to more easily reveal genetic linkage. METHODS: From a collection of 160 pedigrees multiplex for SLE, we selected 36 pedigrees that also contained >or=2 members with self-reported RA (19 pedigrees were African American, 14 were European American, and 3 were of other ethnic origin). Data from a genome scan of 307 microsatellite markers were evaluated for SLE linkage by contemporary genetic epidemiologic techniques. RESULTS: The most significant evidence of linkage to SLE was obtained at 5p15.3 in the European American pedigrees by both parametric (logarithm of odds [LOD] score 6.2, P = 9.3 x 10(-8)) and nonparametric (LOD score 6.9, P = 1.7 x 10(-8)) methods. The best-fitting model for this putative SLE gene in this region was a recessive gene with a population frequency of 5% and with 50% penetrance in females and 15% penetrance in males at virtually 100% homogeneity. CONCLUSION: For a genetically complex disease phenotype, an unusually powerful linkage has been found with SLE at 5p15.3 in European American pedigrees multiplex for SLE and for self-reported RA. This result predicts the presence of a gene at the top of chromosome 5 in this subset of patients that is important for the pathogenesis of SLE. 相似文献
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Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis 下载免费PDF全文
Scott C. Kolbe Trevor J. Kilpatrick Peter J. Mitchell Owen White Gary F. Egan Joanne Fielding 《Human brain mapping》2014,35(5):2310-2319
Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing–remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray‐matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel‐wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region‐wise regression analyses confirmed that AS errors also correlated with gray‐matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Hum Brain Mapp 35:2310–2319, 2014. © 2013 Wiley Periodicals, Inc . 相似文献
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