全文获取类型
收费全文 | 345篇 |
免费 | 25篇 |
出版年
2023年 | 2篇 |
2022年 | 10篇 |
2021年 | 8篇 |
2020年 | 1篇 |
2019年 | 9篇 |
2018年 | 11篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 18篇 |
2014年 | 18篇 |
2013年 | 36篇 |
2012年 | 20篇 |
2011年 | 31篇 |
2010年 | 14篇 |
2009年 | 21篇 |
2008年 | 29篇 |
2007年 | 30篇 |
2006年 | 18篇 |
2005年 | 8篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
排序方式: 共有370条查询结果,搜索用时 15 毫秒
1.
A Hennig R Krueger D Mangoura N B Schwartz 《Cellular and molecular biology, including cyto-enzymology》1992,38(5-6):585-593
Proteoglycans of developing chick brain were distinguished on the basis of reactivity with four well characterized antibody reagents (S103L, to the CS-rich domain; HNK-1, to 6-sulfated glucuronic acid; 1-C-3, to the HABr region and 5-D-4, to KS chains). One chondroitin sulfate proteoglycan reacted exclusively with S103L and 1-C-3 and not with the other two antibodies, hence is designated the S103L reactive brain CSPG. The other proteoglycan reacted exclusively with HNK-1 and 5-D-4 and not with S103L and 1-C-3, hence it is designated the HNK-1 reactive brain CSPG. In addition to these immunological distinctions, the S103L and HNK-1 CSPGs exhibited significant biochemical differences at both the protein and carbohydrate levels. Most interestingly, both CSPGs were found in all regions of the brain, and were expressed in a developmentally regulated pattern. The S103L CSPG was not detectable prior to embryonic day 7, increased to a maximum at day 13-15 and declined by day 20 in most brain regions examined. In contrast, the HNK-1 CSPG was present as early as embryonic day 4 and remained constant through hatching. Neuronal cultures established from embryonic day 6 (E6) cerebral hemispheres represent an in vitro paradigm that mimics in vivo neuronal development and differentiation. In this culture system we found that the expression of the S103L and HNK-1 CSPG followed a pattern similar to that observed in developing brain and further, that neurons are probably the sole source of S103L CSPG in cerebral cortex during neuroembryogenesis. 相似文献
2.
Sotirios G. Doukas Panagiotis G. Doukas Clarence T. Sasaki Dimitra Vageli 《Journal of cellular and molecular medicine》2020,24(18):10311-10321
Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre‐clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF‐κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF‐κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 μmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF‐κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile‐induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF‐κB, and shaping future translational development of effective targeted therapies using topical non‐pharmacologic inhibitors of NF‐κB. 相似文献
3.
4.
Paschalia Kapli Dimitra Botoni Çetin Ilgaz Yusuf Kumlutaş Aziz Avcı Nasrullah Rastegar-Pouyani Behzad Fathinia Petros Lymberakis Faraham Ahmadzadeh Nikos Poulakakis 《Molecular phylogenetics and evolution》2013,66(3):992-1001
Apathya is a lacertid genus occurring mainly in south-east Turkey and its adjacent regions (part of Iran and Iraq). So far two morphological species have been attributed to the genus; A. cappadocica (with five subspecies, A. c. cappadocica, A. c. muhtari, A. c. schmidtlerorum, A. c. urmiana and A. c. wolteri) and A. yassujica. The first species occupies most of the genus’ distribution range, while A. yassujica is endemic of the Zagros Mountains. Here, we explored Apathya’s taxonomy and investigated the evolutionary history of the species by employing phylogenetic and phylogeographic approaches and using both mitochondrial (mtDNA) and nuclear markers. The phylogenetic relationships and the genetic distances retrieved, revealed that Apathya is a highly variable genus, which parallels its high morphological variation. Such levels of morphological and genetic differentiation often exceed those between species of other Lacertini genera that are already treated as full species, suggesting the necessity for a taxonomic revision of Apathya. The phylogeographical scenario emerging from the genetic data suggests that the present distribution of the genus was determined by a combination of dispersal and vicariance events between Anatolia and Southwest Asia dating back to the Miocene and continuing up to the Pleistocene. Key geological events for the understanding of the phylogeography of the genus are the movement of the Arabian plate that led to the configuration of Middle East (orogenesis of the mountain ranges of Turkey and Iran) and the formation of Anatolian Diagonal. 相似文献
5.
Dr Christos A. Kontogiorgis Yanan Xu Dimitra Hadjipavlou-Litina Yuan Luo 《Free radical research》2013,47(10):1168-1180
The role of oxidative stress and free radicals in the development of Alzheimer's disease (AD) has been the focus of many recent studies. The role of hydrogen peroxide (H2O2) in AD is thought to be associated with Aβ (amyloid – β) damage in cells. A number of coumarin derivatives were previously found to be potent anti-inflammatory and antioxidant agents. Herein, these coumarin derivatives were tested as H2O2 scavengers with the DCF assay using two types of neuronal cells: (a) wild type (N2a) neuroblastoma cells and (b) APP/PS1 transgenic cell line expressing Aβ. Their scavenging activity was varied between the types of cell cultures and it was found to be concentration and time dependent in the mutant cells. Their protective role against cell death further supports this notion. These results suggest that these compounds could be used as a template in the design of new molecules with a possible role in AD. 相似文献
6.
Christos Kontogiorgis Dimitra Hadjipavlou-Litina 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):63-69
Several linear and angular coumarins designed and synthesised as possible anti-inflammatory and antioxidant agents were evaluated for their biological activities, using the carrageenin-induced rat paw oedema model. In general, the compounds were found to be potent anti-inflammatory agents. Compound (4) was found to possess protective properties in adjuvant-induced arthritis in rats. The compounds were found to interact with 1,1-diphenyl-2-picryl-hydrazyl stable free radical (DPPH) whereas most of them were essentially inactive in other tests. The anti-inflammatory activity seemed to be connected with their reducing activity. R M values were determined as an expression of their lipophilicity which was also calculated as clog P. Only a poor relationship existed between lipophilicity and anti-inflammatory activity. 相似文献
7.
Laminin 332 is an essential component of the dermal-epidermal junction, a highly specialized basement membrane zone that attaches the epidermis to the dermis and thereby provides skin integrity and resistance to external mechanical forces. Mutations in the LAMA3, LAMB3 and LAMC2 genes that encode the three constituent polypeptide chains, α3, β3 and γ2, abrogate or perturb the functions of laminin 332. The phenotypic consequences are diminished dermal-epidermal adhesion and, as clinical symptoms, skin fragility and mechanically induced blistering. The disorder is designated as junctional epidermolysis bullosa (JEB). This article delineates the signs and symptoms of the different forms of JEB, the mutational spectrum, genotype-phenotype correlations as well as perspectives for future molecular therapies. 相似文献
8.
Dimitrios Paraskevis Georgios Nikolopoulos Anastasios Fotiou Chrissa Tsiara Dimitra Paraskeva Vana Sypsa Marios Lazanas Panagiotis Gargalianos Mina Psichogiou Athanasios Skoutelis Lucas Wiessing Samuel R. Friedman Don C. d. e. s. Jarlais Manina Terzidou Jenny Kremastinou Meni Malliori Angelos Hatzakis 《PloS one》2013,8(11)
Background
During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak.Methods
Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008–2012).Results
IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998–2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in “new” drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008–2012 (economic recession) compared with 2002–2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008–2012 and 1998–2007, respectively. The coverage of harm reduction services was low throughout the study period.Conclusions
Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur. 相似文献9.
Jennifer R. Bellon Frank Schmid Dimitra L. Capone Barbara L. Dunn Paul J. Chambers 《PloS one》2013,8(4)
Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment. 相似文献
10.