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31.
Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimer's disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients. 相似文献
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目的研究特异性激动APP/PS1转基因小鼠脑组织中α7神经型尼古丁受体(α7 nAChR)水平后对海马组织DYN-Ⅰ蛋白的影响;探讨α7 nAChR在阿尔茨海默病(Alzheimer disease,AD)发病机制中的神经保护作用机制。方法实验动物分为对照组(Control)、野生加PNU282987组(WP)、APP/PS1转基因组(APP/PS1)和APP/PS1加PNU282987组(AP)各8只,WP和AP组给予α7 nAChRs特异性激动剂PNU-282987,另两组给予生理盐水,给药方式为小鼠24 w龄时1 mg/kg腹腔注射PNU-282987,连续5 d。采用Real-time PCR法和蛋白免疫印迹(Western Blot)法分别测定小鼠海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白表达水平的变化。结果与control组相比,APP/PS1组海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平下降(P0.05,P0.01);而特异性激动α7 nAChR水平后,与对照组相比WP组中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平升高(P0.05,P0.01);与APP/PS1组相比AP组小鼠大脑海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平明显升高(P0.01,P0.01)。结论特异性激动APP/PS1转基因小鼠海马组织中α7 nAChR水平能够使网格蛋白内吞调节蛋白DYN-Ⅰ表达升高。这可能提示了α7 nAChR对突触有一定的保护作用,进一步说明α7 nAChR在阿尔茨海默病的发病中起着重要作用。 相似文献
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希罗达联合奥沙利铂治疗老年转移性结直肠癌 总被引:3,自引:0,他引:3
[目的]观察希罗达联合奥沙利铂治疗老年(≥70岁)转移性结直肠癌患者的疗效及不良反应.[方法]采用XELOX方案治疗23例老年转移性结直肠癌,d1予奥沙利铂130 mg/m2,d1~14希罗达1 000 mg/(m2·d)口服,2次/天,3周1个周期,至少2个周期.[结果]23例患者中,完全缓解1例(4%),部分缓解9例(39%),稳定8例(35%),肿瘤进展5例(22%).总有效率为43%(10/23),中位肿瘤进展时间8.1(6.7~11.1)个月,中位总生存期13.9(10.9~17.2)个月.最常见的不良反应为消化道反应、骨髓抑制、神经感觉障碍及手足综合征,多为Ⅰ~Ⅱ度.[结论]XELOX是治疗老年转移性结直肠癌安全有效的化疗方案. 相似文献
36.
Hiromi Mizutani Risa Tamagawa-Mineoka Naomi Nakamura Koji Masuda Norito Katoh 《Allergology international》2017,66(3):440-444
Background
Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients.Methods
We measured the serum IL-21 levels of adult AD patients and healthy control subjects using an enzyme-linked immunosorbent assay.Results
The adult AD patients exhibited significantly higher serum IL-21 levels than the healthy control subjects. A comparison of the patients' serum IL-21 levels based on the clinical severity of their AD revealed that the patients with severe AD demonstrated significantly higher serum IL-21 levels than those with mild AD and the healthy control subjects. The serum IL-21 levels were significantly correlated with the skin severity score, and especially with the degree of acute lesions such as erythema and edema/papules. The serum IL-21 level was not associated with laboratory markers, such as the serum IgE level, the serum thymus and activation-related chemokine level, blood eosinophilia, and the serum lactate dehydrogenase level.Conclusions
These results suggest that IL-21 might be involved in the pathogenesis of AD, especially the development of acute skin lesions. 相似文献37.
Wendy F. Davidson Donald Y.M. Leung Lisa A. Beck Cecilia M. Berin Mark Boguniewicz William W. Busse Talal A. Chatila Raif S. Geha James E. Gern Emma Guttman-Yassky Alan D. Irvine Brian S. Kim Heidi H. Kong Gideon Lack Kari C. Nadeau Julie Schwaninger Angela Simpson Eric L. Simpson Marshall Plaut 《The Journal of allergy and clinical immunology》2019,143(3):894-913
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Julius Sipil Harri Nurmi Ann Marie Kaukonen Jouni Hirvonen Jyrki Taskinen Jari Yli-Kauhaluoma 《European journal of pharmaceutical sciences》2005,25(4-5):417-425
Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature – current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pKa's for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pKa of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r2 = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols. 相似文献
40.
Montey Garg Ben Tudor-Green Brian Bisase 《The British journal of oral & maxillofacial surgery》2019,57(8):711-715
Metastasis to the neck in patients with oral squamous cell carcinoma (SCC) has a huge impact on long-term survival and prognosis, and its incidence varies. Due consideration therefore should be given to management of the neck in each individual case. The pathways in patients with primary oral SCC are well-established, but there is a paucity of published papers on management of the neck in those with ipsilateral recurrent or second primary oral SCC whose necks have previously been operated on with or without radiotherapy or chemoradiotherapy, or treated with radiotherapy or chemoradiotherapy alone. These patients may be under treated because of failure to stage the most likely drainage site, and are likely to have a worse outcome if there is macroscopic recurrence in the neck after independent treatment of the recurrent or second primary tumour. Based on the current review, we think there is a need for a multicentre, collaborative, retrospective review of the outcomes of patients with ipsilateral second primaries or recurrent oral SCC in the previously treated neck. Our recommendations include consideration of positron emission tomography-computed tomography in all patients with recurrent or second primary oral SCC (if “hot” – neck dissection, if “cold” - sentinel node biopsy); consideration of sentinel node biopsy in all patients with recurrent or second primary oral SCC who have previously had treatment to the neck; and finally, consideration of definitive management of the sentinel biopsy zone or region if the node is invaded. 相似文献