全文获取类型
收费全文 | 619篇 |
免费 | 27篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 33篇 |
妇产科学 | 7篇 |
基础医学 | 72篇 |
口腔科学 | 16篇 |
临床医学 | 98篇 |
内科学 | 138篇 |
皮肤病学 | 32篇 |
神经病学 | 20篇 |
特种医学 | 127篇 |
外科学 | 17篇 |
综合类 | 22篇 |
预防医学 | 23篇 |
眼科学 | 4篇 |
药学 | 15篇 |
1篇 | |
肿瘤学 | 23篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 19篇 |
2012年 | 10篇 |
2011年 | 16篇 |
2010年 | 29篇 |
2009年 | 33篇 |
2008年 | 15篇 |
2007年 | 25篇 |
2006年 | 19篇 |
2005年 | 17篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2001年 | 13篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 37篇 |
1997年 | 45篇 |
1996年 | 38篇 |
1995年 | 19篇 |
1994年 | 29篇 |
1993年 | 22篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 22篇 |
1988年 | 20篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 14篇 |
1983年 | 14篇 |
1982年 | 12篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1969年 | 1篇 |
排序方式: 共有651条查询结果,搜索用时 15 毫秒
61.
The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components. 相似文献
62.
To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation. 相似文献
63.
A Choppin I Irwin L Lach MG McDonald AE Rettie L Shao C Becker MP Palme X Paliard S Bowersox DM Dennis P Druzgala 《British journal of pharmacology》2009,158(6):1536-1547
Background and purpose:
Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.Experimental approach:
Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).Key results:
Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K1 treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.Conclusions and implications:
Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients. 相似文献64.
Development of the Manchester framework for the evaluation of emergency department pharmacy services
Greenwood D Tully MP Martin S Steinke D 《International journal of clinical pharmacy》2022,44(4):930-938
International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as... 相似文献
65.
Treatment of vitiligo with topical imiquimod 总被引:1,自引:0,他引:1
66.
T Canedo MP De Almeida T Cuzzi M Ramos‐e‐Silva 《Journal of the European Academy of Dermatology and Venereology》2010,24(2):178-185
Background Some adnexal tumours have many controversies about their histogenesis. Objectives To evaluate the eccrine and/or apocrine differentiation phenotype in cases of cylindroma and clear cell hidradenoma with CD15 and p63 antibodies. Methodology Slides and blocks of six cases of cylindroma and seven cases of nodular hidradenoma (clear cells) were analyzed by the technique of immunohistochemistry with CD15 and p63 antibodies. Results In all cases of cylindroma we obtained negative results for CD15 antibody and positive for p63 antibody. In five of seven cases of nodular hidradenoma (clear cell), we could easily observe clear cells between 20% and 50% of tumour cells. In the two other cases, cystic lesions were present and occasional clear cells could be seen. The reaction with CD15 antibody was positive in granular and cytoplasmic pattern in six of seven cases, especially in cells with suggestive clear cytoplasm in lower proportion than this clear cells could be seen in haematoxylin and eosin. The positivity for p63 antibody, nuclear pattern, was observed in six of seven cases, in the major part of tumour cells. In only one case, the positivity was in 20% of cells. Limitation Samples are in small number because these are relatively rare tumours. Conclusions The present study suggests eccrine origin for both tumours: cylindroma and clear cell hidradenoma. 相似文献
67.
68.
MA Vieira-Coelho MP Serr?o J Afonso CE Pinto E Moura 《British journal of pharmacology》2009,158(3):726-737
Background and purpose:
This study investigates the role of α2-adrenoceptor subtypes, α2A, α2B and α2C, on catecholamine synthesis and catabolism in the central nervous system of mice.Experimental approach:
Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from α2A-, α2B- and α2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice.Key results:
Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in α2A- and α2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α2A and α2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue)−1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in α2A and α2CKO [WT: 40 ± 1; α2A: 77 ± 2; α2B: 40 ± 1; α2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein)−1·h−1], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α2KO mice [WT: 2.0 ± 0.0; α2A: 2.4 ± 0.1; α2B: 2.2 ± 0.0; α2C: 2.2 ± 0.0 nmol·(mg protein)−1·h−1], but no significant differences were found in monoamine oxidase activity between all α2KOs and WT mice.Conclusions and implications:
In mouse brain, deletion of α2A- or α2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α2-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α2A and α2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. 相似文献69.
Morphological studies have shown that macrophages and microglia undergo
apoptosis in the central nervous system (CNS) in acute experimental
autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative
levels of macrophage and microglial apoptosis, and the molecular mechanisms
involved in this process, we used three-colour flow cytometry to identify
CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the
inflammatory cells isolated from the spinal cords of Lewis rats 13 days
after immunization with myelin basic protein (MBP) and complete Freund's
adjuvant. Simultaneously, we analyzed the DNA content of these cell
populations to assess the proportions of cells undergoing apoptosis and in
different stages of the cell cycle or examined their expression of three
apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and
Bcl-2. Microglia were highly vulnerable to apoptosis and were
over-represented in the apoptotic population. Macrophages were less
susceptible to apoptosis than microglia and underwent mitosis more
frequently than microglia. The different susceptibilities of microglia and
macrophages to apoptosis did not appear to be due to variations in Fas,
FasL or Bcl- 2 expression, as the proportions of microglia and macrophages
expressing these proteins were similar, and were relatively high.
Furthermore, in contrast to T cell apoptosis, apoptosis of
microglia/macrophages did not occur more frequently in cells expressing Fas
or FasL, or less frequently in cells expressing Bcl-2. These results
indicate that the apoptosis of microglia and CNS macrophages in EAE is not
mediated through the Fas pathway, and that Bcl-2 expression does not
protect them from apoptosis. Expression of FasL by macrophages and
microglia may contribute to the pathogenesis and immunoregulation of EAE
through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high
level of microglial apoptosis in EAE indicates that microglial apoptosis
may be an important homeostatic mechanism for controlling the number of
microglia in the CNS following microglial activation and proliferation.
相似文献
70.
F Gallardo MP García-Muret O Servitje T Estrach I Bielsa A Salar E Abella C Barranco RM Pujol 《Journal of the European Academy of Dermatology and Venereology》2009,23(6):639-647
Background The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30+ cutaneous T-cell lymphoma (2 patients), CD4+ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.
None declared. 相似文献
Objective This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30
Results The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.
Conflicts of interest
None declared. 相似文献