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31.
Svetlana Zhdanova Scott K. Heysell Oleg Ogarkov Galina Boyarinova Galina Alexeeva Suporn Pholwat Elena Zorkaltseva Eric R. Houpt Eugeniy Savilov 《Emerging infectious diseases》2013,19(10):1649-1652
Of 235 Mycobacterium tuberculosis isolates from patients who had not received tuberculosis treatment in the Irkutsk oblast and the Sakha Republic (Yakutia), eastern Siberia, 61 (26%) were multidrug resistant. A novel strain, S 256, clustered among these isolates and carried eis-related kanamycin resistance, indicating a need for locally informed diagnosis and treatment strategies. 相似文献
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Neelima Afroz Molla Kabirul Ahsan Mollah Waranya Wongwit Oleg Shipin Pongrama Ramasoota 《Archives of environmental & occupational health》2017,72(6):336-342
This study quantifies the diarrhea burden among migrant children under age 5 (who have migrated due to environmental degradation) in Dhaka. We used a multifactor socioepidemiological as well as environmental approach with pretested questionnaires and observations. It was found that 52% of the children were affected by diarrhea. Disability-adjusted life years (DALYs) lost was reduced manifold with the increase of mothers' behavioral determinants. Health losses were 1,718 fold with significant coefficient (β) in the migrant group. DALYs lost were significantly associated with socioenvironmental factors such as mother's illiteracy (β = .18; p < .001), no hand wash before eating (β = .08; p = .004), and no hand wash after defecation (β = .10; p < .001). This puts emphasis clearly on the awareness at household level, especially of mothers and children under age 5 in Dhaka, Bangladesh, in formulating migration-related policies. 相似文献
35.
Gennady Bratslavsky Stephanie Gleicher Joseph M. Jacob Thomas H. Sanford Oleg Shapiro Dimitra Bourboulia Laurie M Gay Julie Andrea Elvin Jo-Anne Vergilio James Suh Shakti Ramkissoon Eric Allan Severson Jonathan Keith Killian Alexa Betzig Schrock Jon H. Chung Vincent A. Miller Mehdi Mollapour Jeffrey S. Ross 《Urologic oncology》2021,39(6):367.e1-367.e5
Introduction and ObjectiveUnlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.Material and MethodsDNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626). Comprehensive genomic profiling was performed, and Tumor mutational burden (TMB) and microsatellite instability (MSI) were calculated. We analyzed all classes of genomic alterations.ResultsmCDC had 1.7 versus 2.7 genomic alterations/tumor in mCCRCC ( = 0.04). Mutations in VHL (P < 0.0001) and TSC1 (P = 0.04) were more frequent in mCCRCC. SMARCB1 (P < 0.0001), NF2 (P = 0.0007), RB1 (P = 0.02) and RET (P = 0.0003) alterations were more frequent in mCDC versus mCCRCC. No VHL alterations in mRMC and mCDC were identified. SMARCB1 genomic alterations were significantly more frequent in mRMC than mCDC (P = 0.0002), but were the most common alterations in both subtypes. Mutations to EGFR, RET, NF2, and TSC2 were more frequently identified in mCDC versus mRMC. The median TMB and MSI-High status was low with <1% of mCCRC, mCDC, and mRMC having ≥ 20 mut/Mb.ConclusionGenomic alteration patterns in mCDC and mRMC differ significantly from mCCRCC. Targeted therapies for mCDC and mRMC appear limited with rare opportunities to target alterations in receptor tyrosine kinase and MTOR pathways. Similarly, TMB and absence of MSI-High status in mCDC and mRMC suggest resistance to immunotherapies. 相似文献
36.
Denis A. Mogilenko Oleg Shpynov Prabhakar Sairam Andhey Laura Arthur Amanda Swain Ekaterina Esaulova Simone Brioschi Irina Shchukina Martina Kerndl Monika Bambouskova Zhangting Yao Anwesha Laha Konstantin Zaitsev Samantha Burdess Susan Gillfilan Sheila A. Stewart Marco Colonna Maxim N. Artyomov 《Immunity》2021,54(1):99-115.e12
37.
Natalia S. Kozhevnikova Tatyana I. Gorbunova Andrey S. Vorokh Marina G. Pervova Alexsander Ya. Zapevalov Victor I. Saloutin Oleg N. Chupakhin 《Sustainable Chemistry and Pharmacy》2019
The chemical stability and hydrophobic nature of chloroarenes make them a persistent environmental hazard. Modeling of 1,2,4-trichlorobenzene (1,2,4-TCB) degradation in alcohol-water solution under UV irradiation was carried out with the aim of probing how the 1,2,4-TCB might behave in the environment. The photocatalytic activity of both bare TiO2 and TiO2 doped by colloidal CdS nanoparticles synthesized by the sol-gel method has been investigated in the processes of 1,2,4-TCB photodegradation in the aqueous protic solvent. Non-sensitized TiO2 cannot be regarded as catalyst for the 1,2,4-TCB photodecomposition. On the contrary, the CdS/TiO2 composite accelerated the 1,2,4-TCB photodegradation process. The concentration of CdS/TiO2 was shown to effect on the 1,2,4-TCB photolysis mechanisms, which resulted in the quantitative ratios of the 1,2,4-TCB photolysis products. 相似文献
38.
Oleg V. Grinchuk Efthymios Motakis Surya Pavan Yenamandra Ghim Siong Ow Piroon Jenjaroenpun Zhiqun Tang Aliaksandr A. Yarmishyn Anna V. Ivshina Vladimir A. Kuznetsov 《Oncotarget》2015,6(39):42197-42221
More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers. 相似文献
39.
The phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease 下载免费PDF全文
Gorbatyuk OS Li S Sullivan LF Chen W Kondrikova G Manfredsson FP Mandel RJ Muzyczka N 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(2):763-768
Studies have shown that alpha-synuclein (alpha-syn) deposited in Lewy bodies in brain tissue from patients with Parkinson disease (PD) is extensively phosphorylated at Ser-129. We used recombinant Adeno-associated virus (rAAV) to overexpress human wild-type (wt) alpha-syn and two human alpha-syn mutants with site-directed replacement of Ser-129 to alanine (S129A) or to aspartate (S129D) in the nigrostriatal tract of the rat to investigate the effect of Ser-129 phosphorylation state on dopaminergic neuron pathology. Rats were injected with rAAV2/5 vectors in the substantia nigra pars compacta (SNc) on one side of the brain; the other side remained as a nontransduced control. The level of human wt or mutant alpha-syn expressed on the injected side was about four times the endogenous rat alpha-syn. There was a significant reduction of dopaminergic neurons in the SNc and dopamine (DA) and tyrosine hydroxylase (TH) levels in the striatum of all S129A-treated rats as early as 4 wk postinjection. Nigral DA pathology occurred more slowly in the wt-injected animals, but by 26 wk the wt alpha-syn group lost nigral TH neurons equivalent to the mutated S129A group at 8 wk. In stark contrast, we did not observe any pathological changes in S129D-treated animals. Therefore, the nonphosphorylated form of S129 exacerbates alpha-syn-induced nigral pathology, whereas Ser-129 phosphorylation eliminates alpha-syn-induced nigrostriatal degeneration. This suggests possible new therapeutic targets for Parkinson Disease. 相似文献