全文获取类型
收费全文 | 1072篇 |
免费 | 46篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 41篇 |
妇产科学 | 18篇 |
基础医学 | 244篇 |
口腔科学 | 17篇 |
临床医学 | 101篇 |
内科学 | 126篇 |
皮肤病学 | 22篇 |
神经病学 | 88篇 |
特种医学 | 96篇 |
外科学 | 88篇 |
综合类 | 8篇 |
预防医学 | 87篇 |
眼科学 | 8篇 |
药学 | 88篇 |
中国医学 | 13篇 |
肿瘤学 | 71篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 24篇 |
2020年 | 17篇 |
2019年 | 25篇 |
2018年 | 34篇 |
2017年 | 24篇 |
2016年 | 28篇 |
2015年 | 33篇 |
2014年 | 51篇 |
2013年 | 76篇 |
2012年 | 109篇 |
2011年 | 98篇 |
2010年 | 41篇 |
2009年 | 34篇 |
2008年 | 92篇 |
2007年 | 113篇 |
2006年 | 82篇 |
2005年 | 50篇 |
2004年 | 47篇 |
2003年 | 36篇 |
2002年 | 36篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有1120条查询结果,搜索用时 15 毫秒
1.
Iva Justini Ana Kati Deni Uri
i Boena urko‐Cofek Branka Blagovi Gordana anadi Jurei 《Environmental toxicology》2020,35(3):346-358
The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl‐CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment. 相似文献
2.
Gordana Kocic Gordana Bjelakovic Dusica Pavlovic Tatjana Jevtovic Voja Pavlovic Dusan Sokolovic Jelena Basic Snezana Cekic Tatjana Cvetkovic Radivoj Kocic Svetlana Stojanovic 《Hepatology research》2007,37(8):637-646
Aim: Fas membrane-associated polypeptide antigen is a receptor molecule responsible for apoptosis-mediated signals. In animal models of acute viral hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors; therefore, the aim of this study was to evaluate the effect of interferon (IFN)-alpha on apoptotic markers and nuclease activity against different coding and non-coding single and double stranded RNAs during Fas-induced liver apoptosis. Methods: An in vivo experiment was performed with simultaneous administration of anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha. Results: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic events and progression toward late apoptosis after anti-Fas antibody treatment. IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis by increasing the number of viable cells and decreasing the number of cells in late apoptosis, by increasing the percentage of Bcl-2 positive cells, by decreasing the percentage of Bax positive cells, and by decreasing the nuclease activity compared to the anti-Fas antibody treated group. Total DNA and RNA concentration was much reduced in the Fas group and DNA fragmentation assay provided evidence for increased DNA degradation. Enhanced nuclease activity against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was manifested in the anti-Fas antibody treated group, except for the inhibitory-bound alkaline RNase. Conclusions: The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases. 相似文献
3.
Osteogenic differentiation of human bone marrow stromal cells on partially demineralized bone scaffolds in vitro 总被引:11,自引:0,他引:11
Mauney JR Blumberg J Pirun M Volloch V Vunjak-Novakovic G Kaplan DL 《Tissue engineering》2004,10(1-2):81-92
Tissue engineering has been used to enhance the utility of biomaterials for clinical bone repair by the incorporation of an osteogenic cell source into a scaffold followed by the in vitro promotion of osteogenic differentiation before host implantation. In this study, three-dimensional, partially demineralized bone scaffolds were investigated for their ability to support osteogenic differentiation of human bone marrow stromal cells (BMSCs) in vitro. Dynamic cell seeding resulted in homogeneous cell attachment and infiltration within the matrix and produced significantly higher seeding efficiencies when compared with a conventional static seeding method. Dynamically seeded scaffolds were cultured for 7 and 14 days in the presence of dexamethasone and evaluated on biochemical, molecular, and morphological levels for osteogenic differentiation. Significant elevation in alkaline phosphatase activity was observed versus controls over the 14-day culture, with a transient peak indicative of early mineralization on day 7. On the basis of RT-PCR, dexamethasone-treated samples showed elevations in alkaline phosphatase and osteocalcin expression levels at 7 and 14 days over nontreated controls, while bone sialoprotein was produced only in the presence of dexamethasone at 14 days. Scanning electron microscopy evaluation of dexamethasone-treated samples at 14 days revealed primarily cuboidal cells indicative of mature osteoblasts, in contrast to nontreated controls displaying a majority of cells with a fibroblastic cell morphology. These results demonstrate that partially demineralized bone can be successfully used with human BMSCs to support osteogenic differentiation in vitro. This osseous biomaterial may offer new potential benefits as a tool for clinical bone replacement. 相似文献
4.
Anatomical variations in the dimensions of different brain structures have been correlated with clinical syndromes. This study on the parameters of normal and abnormal cavum septi pellucidi (CSP) can be of clinical significance. We obtained 479 brains from autopsied persons (310 males and 169 females, 377 normal or asymptomatic and 102 abnormal or symptomatic persons, aged 22-89 years) and observed that 110 brains (75 males and 35 females) had CSP. These cava were classified into two groups depending on the past medical histories of the autopsied person: 40 asymptomatic and 70 symptomatic cava. We have defined symptomatic cava as those in autopsied persons who had known past medical history of psychiatric or neurological disease. Asymptomatic cava were in autopsied persons who had no known past medical history of psychiatric or neurological disease. The CSP parameters (length, width, depth) of the symptomatic and asymptomatic groups were measured and were statistically analyzed. Analysis showed that the cava in the symptomatic group were significantly longer and wider. Discriminant function analysis was used to derive a mathematical formula to classify CSP into an asymptomatic or symptomatic group based on length and width measurements of the cavum. 相似文献
5.
Large B-cell lymphomas (LBCLs) have significant false-negative results when immunophenotyped by flow cytometry (FC). To clarify the role fine-needle aspiration (FNA) in reducing this false-negative rate, 28 cases ultimately diagnosed as LBCL that had FNA as part of the workup and a negative FC were identified. We examined their clinical and cytologic features, in comparison with cases of LBCL with FNAs that were positive by FC. In 24/28 FC-negative cases (86%) a cytologic diagnosis of suspicious or positive for malignancy was rendered. We conclude that cytologic analysis is more sensitive than FC in the diagnosis of malignancy in FNA of LBCL, particularly in aspirates with low cellularity and/or low viability. Examination of cytospin preparations of the actual material analyzed by FC may provide an indication that an FC result is falsely negative. It is important to recognize the potential of false-negativity by FC of LBCLs when interpreting FNAs with features suggesting lymphoma. 相似文献
6.
Differential effects of growth factors on tissue-engineered cartilage 总被引:18,自引:0,他引:18
Blunk T Sieminski AL Gooch KJ Courter DL Hollander AP Nahir AM Langer R Vunjak-Novakovic G Freed LE 《Tissue engineering》2002,8(1):73-84
The effects of four regulatory factors on tissue-engineered cartilage were examined with specific focus on the ability to increase construct growth rate and concentrations of glycosaminoglycans (GAG) and collagen, the major extracellular matrix (ECM) components. Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured in medium with or without supplemental insulin-like growth factor (IGF-I), interleukin-4 (IL-4), transforming growth factor-beta1 (TGF-beta1) or platelet-derived growth factor (PDGF). IGF-I, IL-4, and TGF-beta1 increased construct wet weights by 1.5-2.9-fold over 4 weeks of culture and increased amounts of cartilaginous ECM components. IGF-I (10-300 ng/mL) maintained wet weight fractions of GAG in constructs seeded at high cell density and increased by up to fivefold GAG fractions in constructs seeded at lower cell density. TGF-beta1 (30 ng/mL) increased wet weight fractions of total collagen by up to 1.4-fold while maintaining a high fraction of type II collagen (79 plus minus 11% of the total collagen). IL-4 (1-100 ng/mL) minimized the thickness of the GAG-depleted region at the construct surfaces. PDGF (1-100 ng/mL) decreased construct growth rate and ECM fractions. Different regulatory factors thus elicit significantly different chondrogenic responses and can be used to selectively control the growth rate and improve the composition of engineered cartilage. 相似文献
7.
8.
Christine R. Critchley Jennifer Fleming Dianne Nicol Paula Marlton Megan Ellis Lisa Devereux Gordana Bruce Ian Kerridge 《European journal of human genetics : EJHG》2021,29(3):503
Various forms of private investment are considered necessary for the sustainability of biobanks, yet pose significant challenges to public trust. To manage this tension, it is vital to identify the concerns of relevant stakeholders to ensure effective and acceptable policy and practice. This research examines the aspects of commercialisation that are of most concern to the Australian public (n = 800) and patients who had donated their tissue to two large disease specific (cancer) public biobanks (n = 564). Overall, we found a commercialisation effect (higher support for public relative to private) in relation to funding, research location and access to stored biospecimens. The effect was strongest for research locations and access compared to funding. A latent class analysis revealed the pattern of concern differed, with the majority (34.1%) opposing all aspects of commercialisation, a minority supporting all (15.7%), one quarter (26.8%) opposing some (sharing and selling tissue) but not others (research locations and funding), and a group who were unsure about most aspects but opposed selling tissue (23.5%). Patient donors were found to be more accepting of and unsure about most aspects of commercialisation. Members of the (general) public who were motivated to participate in biobanking were more likely to oppose some aspects while supporting others, while those who indicated they would not donate to a biobank were more likely to oppose all aspects of commercialisation. The results suggest that approaches to policy, engagement and awareness raising need to be tailored for different publics and patient groups to increase participation.Subject terms: Genetics research, Ethics 相似文献
9.
Justyna D. Kowalska Carlo Biekowski Luk Fleischhans Sergii Antoniak Agata Skrzat-Klapaczyska Magdalena Suchacz Nikolina Bogdanic Deniz Gokengin Cristiana Oprea Igor Karpov Kerstin Kase Raimonda Matulionyte Antonios Papadopoulos Nino Rukhadze Arjan Harxhi David Jilich Botond Lakatos Dalibor Sedlacek Gordana Dragovic Marta Vasylyev Antonia Verhaz Nina Yancheva Josip Begovac Andrzej Horban 《Viruses》2022,14(5)
10.
Maja Misirkic Kristina Janjetovic Ljubica Vucicevic Gordana Tovilovic Biljana Ristic Urosh Vilimanovich Ljubica Harhaji-Trajkovic Mirjana Sumarac-Dumanovic Dragan Micic Vladimir Bumbasirevic Vladimir Trajkovic 《Pharmacological research》2012,65(1):111-119
The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death. 相似文献