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81.
82.
Banaszczyk MG Carlo AT Millan V Lindsey A Moss R Carlo DJ Hendler SS 《Anesthesia and analgesia》2002,95(5):1285-92, table of contents
After a single IV injection of the water-soluble propofol prodrug propofol phosphate (PP) in mice, rats, rabbits, and pigs, propofol was produced rapidly (1-15 min), inducing dose-dependent sedative effects. In mice, the hypnotic dose (HD(50)), lethal dose (LD(50)), and safety index (defined as a ratio: LD(50)/HD(50)) were 165.4 mg/kg, 600.6 mg/kg, and 3.6, respectively. Propofol was produced with half-lives of 5.3 +/- 0.6 min in rats, 2.1 +/- 0.6 min in rabbits, and 4.4 +/- 2.4 min in pigs. The maximal concentration was dose and species dependent. The elimination half-life was 24 +/- 12 min in rats, 21 +/- 16 min in rabbits, and 225 +/- 56 min in pigs. Propofol generated from PP produced pharmacological effects similar to those described in the literature. We found a correlation between PP dose and duration of sedation with propofol concentrations larger than 1.0 microg/mL, which produced somnolence and sedation in rats and pigs. Adequate sedation and, at large enough doses, anesthetic-level sedation were produced after the administration of PP. Overall, PP, the water-soluble prodrug of propofol, seems to be a viable development candidate for sedative and anesthetic applications. IMPLICATIONS: Propofol phosphate, a water-soluble prodrug of the widely used IV anesthetic propofol, was developed and evaluated in mice, rats, rabbits, and pigs after IV injection. The results of the study clearly demonstrate the feasibility of the prodrug approach to achieve sedative and anesthetic levels of propofol in laboratory animals; this warrants further evaluation in humans. 相似文献
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Furlan R Bergami A Lang R Brambilla E Franciotta D Martinelli V Comi G Panina P Martino G 《Journal of neuroimmunology》2000,111(1-2):86-92
Systemic administration of interferon (IFN)-beta has been recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The immunological mechanism by which IFN-beta ameliorates MS is still partially unknown. We measured the number of blood circulating CD4(+), CD4(-), CD8(+), and CD8(-) T cells secreting IFN-gamma and IL-4 in 26 RRMS patients followed for up to 9 months of an alternate day s.c. treatment with 8x16 IU of IFN-beta1b. Compared to pre-treatment values, a significant (P<0.05) reduction of CD4(+), CD4(-), CD8(+) and CD8(-) cells producing IFN-gamma and of CD4(+) and CD4(-) cells producing IL-4 was observed in MS patients. The IFN-beta-associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period. We did not observe any effect of IFN-beta treatment on the percentage of IL-4-producing CD8(+) and CD8(-) cells nor in that of natural killer (NK) cells producing IFN-gamma. Our results show that IFN-beta treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T cells secreting IFN-gamma and IL-4 thus suggesting a broader rather than a specific immunomodulatory effect of IFN-beta in MS. 相似文献
86.
Alaina Kronenberg Francine Blei Emily Ceisler Mark Steele Louis Furlan Sylvia Kodsi 《Journal of AAPOS》2005,9(2):169-173
INTRODUCTION: PHACES syndrome (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects and coarctation of the aorta, Eye abnormalities, and Sternal abnormalities or ventral developmental defects) is a rare neurocutaneous syndrome with only 2 case reports published in the ophthalmic literature. This study was conducted to identify ocular and systemic manifestations of PHACES syndrome. METHODS: A retrospective chart review was performed on 8 children with a diagnosis of PHACES syndrome. Information recorded included age at first visit, length of follow-up, gender, race, vision, need for glasses, strabismus, amblyopia, ptosis, proptosis, anterior and posterior segment abnormalities, need for treatment of the hemangioma, type of treatment of the hemangioma, and systemic manifestations. RESULTS: Periocular and ocular findings in patients with PHACES syndrome included hemangioma involving ocular structures (n = 6), strabismus (n = 4), amblyopia (n = 5), proptosis (n = 2), ptosis (n = 5), anterior polar cataract (n = 1), optic atrophy from optic neuropathy (n = 1), heterochromia (n = 1), and refractive error requiring glasses (n = 2). All patients were treated with steroids for the hemangioma. Systemic manifestations of PHACES syndrome included posterior fossa malformation (n = 4), hemangioma (n = 8), arterial anomalies (n = 3), cardiac abnormalities (n = 3), and sternal or ventral deformities (n = 3). CONCLUSION: Children with PHACES syndrome may have significant ocular and systemic abnormalities and are at increased risk for strabismus and amblyopia. They often require steroid therapy of the hemangioma to prevent and/or treat ocular complications. These patients require careful monitoring by a pediatric ophthalmologist in addition to other subspecialists. 相似文献
87.
The dosing regimen for conversion from cyclosporin A (CsA) to tacrolimus immunosuppression was studied in 12 pediatric liver allograft recipients. Patients were stratified according to their age. Tacrolimus was started orally at a dosage of 0.05 mg/kg b.i.d., 12 h after stopping CsA administration and increased thereafter if needed. Tacrolimus and CsA concentrations were assayed by immunoassay using, respectively, an IMx and a TDx autoanalyzer (Abbott-France). Mean CsA concentration was in the therapeutic range 12 h prior to and at the time of introduction of tacrolimus. After 72 h of tacrolimus therapy, CsA concentrations were undetectable whereas mean tacrolimus concentration was 10.4 ng/mL with a mean dose of 0.09 mg/ kg b.i.d. The decline of CsA concentration was clearly biphasic. A slower decline in CsA concentration was detected after initiation of tacrolimus therapy, suggesting an inhibition of CsA metabolism by tacrolimus. No nephrotoxicity was observed. This dosage regimen allowed effective immunosuppression while avoiding additive nephrotoxicity. 相似文献
88.
Theodore H. Niemann M.D. Tracey L. Trgovac B.S. Violeta R. Mcgaughy M.S. Luis Vaccarello M.D. 《Gynecologic oncology》1996,63(3):318-322
The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death. bcl-2 overexpression was originally described in follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. In this study we used immunohistochemistry to examine bcl-2 protein expression in endometrial hyperplasia and carcinoma. bcl-2 protein was observed in 4/4 cases of complex hyperplasia, 1/4 cases of complex atypical hyperplasia, and 10/29 cases of carcinoma. The staining observed in the cases of complex atypical hyperplasia and carcinoma was focal and less intense than the reactivity of normal proliferative endometrium. We conclude that bcl-2 protein is seldom overexpressed in complex atypical hyperplasia or carcinoma of the endometrium. Rather, in many cases of endometrial carcinoma bcl-2 expression appears to be decreased. 相似文献
89.
Mauro Furlan Gilles Marchal Jean-Michel Derlon Jean-Claude Baron Fausto Viader 《Annals of neurology》1996,40(2):216-226
We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., “penumbral”) tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm·min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p<0.04 to p<0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials. 相似文献