全文获取类型
收费全文 | 182篇 |
免费 | 11篇 |
专业分类
193篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 6篇 |
2015年 | 7篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 8篇 |
2011年 | 7篇 |
2010年 | 11篇 |
2009年 | 12篇 |
2008年 | 8篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 10篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有193条查询结果,搜索用时 0 毫秒
91.
Valentina C Sladky Katja Knapp Tamas G Szabo Vincent Z Braun Laura Bongiovanni Hilda van den Bos Diana CJ Spierings Bart Westendorp Ana Curinha Tatjana Stojakovic Hubert Scharnagl Gerald Timelthaler Kaoru Tsuchia Matthias Pinter Georg Semmler Floris Foijer Alain de Bruin Thomas Reiberger Nataliya RohrUdilova Andreas Villunger 《EMBO reports》2020,21(12)
Polyploidization frequently precedes tumorigenesis but also occurs during normal development in several tissues. Hepatocyte ploidy is controlled by the PIDDosome during development and regeneration. This multi‐protein complex is activated by supernumerary centrosomes to induce p53 and restrict proliferation of polyploid cells, otherwise prone for chromosomal instability. PIDDosome deficiency in the liver results in drastically increased polyploidy. To investigate PIDDosome‐induced p53‐activation in the pathogenesis of liver cancer, we chemically induced hepatocellular carcinoma (HCC) in mice. Strikingly, PIDDosome deficiency reduced tumor number and burden, despite the inability to activate p53 in polyploid cells. Liver tumors arise primarily from cells with low ploidy, indicating an intrinsic pro‐tumorigenic effect of PIDDosome‐mediated ploidy restriction. These data suggest that hyperpolyploidization caused by PIDDosome deficiency protects from HCC. Moreover, high tumor cell density, as a surrogate marker of low ploidy, predicts poor survival of HCC patients receiving liver transplantation. Together, we show that the PIDDosome is a potential therapeutic target to manipulate hepatocyte polyploidization for HCC prevention and that tumor cell density may serve as a novel prognostic marker for recurrence‐free survival in HCC patients. 相似文献
92.
Matthew D. Neal Hongpeng Jia Benjamin Eyer Misty Good Christopher J. Guerriero Chhinder P. Sodhi Amin Afrazi Thomas Prindle Jr Congrong Ma Maria Branca John Ozolek Jeffrey L. Brodsky Peter Wipf David J. Hackam 《PloS one》2013,8(6)
Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. 相似文献
93.
Guerriero C Cairns J Perel P Shakur H Roberts I;CRASH trial collaborators 《PloS one》2011,6(5):e18987
Objective
To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings.Methods
The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.Findings
Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively.Conclusion
Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings.Trial Registration
This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.gov and South African Clinical Trial Register DOH-27-0607-1919. NCT00375258相似文献94.
Preliminary survey of toxicity of the green algaCaulerpa taxifolia introduced into the Mediterranean
R. Lemée D. Pesando M. Durand-Clément A. Dubreuil A. Meinesz A. Guerriero F. Pietra 《Journal of applied phycology》1993,5(5):485-493
Caulerpa taxifolia (Vahl) C. Agardh (Ulvophyceae, Caulerpales) is an alga of tropical origin that was accidentally introduced into the Mediterranean sea in 1984, where this species can reach an abundance that has never been described in tropical endemic regions. It is known that caulerpacean algae can develop an efficient strategy against grazers consisting of the synthesis of repulsive of toxic secondary metabolites: we report here the first study of the toxicity of purified secondary metabolites and raw extracts fromC. taxifolia from the Mediterranean.Toxicity was evaluated on three models: mice (lethality), mammalian cells in culture (cytotoxicity) and sea urchin eggs (disturbance of cell proliferation). Aqueous extracts are only active on fibroblasts and mice. In the three toxicity models a seasonal variation of toxicity is observed for the crude methanol extract as well as a decrease of this activity whenC. taxifolia from the Mediterranean is kept in aquaria. Pure compounds exhibit different toxicity depending on the assay. 10,11-epoxycaulerpenyne is the most active substance on mice and fibroblasts whereas taxifolial A and D are inactive or only weakly toxic. Among the four tested compounds caulerpenyne, the major metabolite ofC. taxifolia, is the most active on sea urchin eggs. Caulerpenyne may therefore represent an ecological risk for microorganisms and the eggs of multicellular animals living close to this alga. The ecological impact of this toxicity on marine organisms and the interaction of this alga with the herbivorous fauna are discussed. 相似文献
95.
96.
Anni 2.0 is an online tool () to aid the biomedical researcher with a broad range of information needs. Anni provides an ontology-based interface to MEDLINE
and retrieves documents and associations for several classes of biomedical concepts, including genes, drugs and diseases,
with established text-mining technology. In this article we illustrate Anni's usability by applying the tool to two use cases:
interpretation of a set of differentially expressed genes, and literature-based knowledge discovery. 相似文献
97.
M Lundervold EJ Milner-Gulland CJ O'Callaghan C Hamblin A Corteyn AP Macmillan 《Acta veterinaria Scandinavica》2004,45(4):211-224
The results of a serological survey of livestock in Kazakhstan, carried out in 1997–1998, are reported. Serum samples from
958 animals (cattle, sheep and goats) were tested for antibodies to foot and mouth disease (FMD), bluetongue (BT), epizootic
haemorrhagic disease (EHD), rinderpest (RP) and peste des petits ruminants (PPR) viruses, and to Brucella spp. We also investigated the vaccination status of livestock and related this to changes in veterinary provision since independence
in 1991. For the 2 diseases under official surveillance (FMD and brucellosis) our results were similar to official data, although
we found significantly higher brucellosis levels in 2 districts and widespread ignorance about FMD vaccination status. The
seroprevalence for BT virus was 23%, and seropositive animals were widespread suggesting endemicity, despite the disease not
having being previously reported. We found a few seropositives for EHDV and PPRV, which may suggest that these diseases are
also present in Kazakhstan. An hierarchical model showed that seroprevalence to FMD and BT viruses were clustered at the farm/village
level, rather than at a larger spatial scale. This was unexpected for FMD, which is subject to vaccination policies which
vary at the raion (county) level. 相似文献
98.
Rajangam AS Kumar M Aspeborg H Guerriero G Arvestad L Pansri P Brown CJ Hober S Blomqvist K Divne C Ezcurra I Mellerowicz E Sundberg B Bulone V Teeri TT 《Plant physiology》2008,148(3):1283-1294
We have identified a gene, denoted PttMAP20, which is strongly up-regulated during secondary cell wall synthesis and tightly coregulated with the secondary wall-associated CESA genes in hybrid aspen (Populus tremula × tremuloides). Immunolocalization studies with affinity-purified antibodies specific for PttMAP20 revealed that the protein is found in all cell types in developing xylem and that it is most abundant in cells forming secondary cell walls. This PttMAP20 protein sequence contains a highly conserved TPX2 domain first identified in a microtubule-associated protein (MAP) in Xenopus laevis. Overexpression of PttMAP20 in Arabidopsis (Arabidopsis thaliana) leads to helical twisting of epidermal cells, frequently associated with MAPs. In addition, a PttMAP20-yellow fluorescent protein fusion protein expressed in tobacco (Nicotiana tabacum) leaves localizes to microtubules in leaf epidermal pavement cells. Recombinant PttMAP20 expressed in Escherichia coli also binds specifically to in vitro-assembled, taxol-stabilized bovine microtubules. Finally, the herbicide 2,6-dichlorobenzonitrile, which inhibits cellulose synthesis in plants, was found to bind specifically to PttMAP20. Together with the known function of cortical microtubules in orienting cellulose microfibrils, these observations suggest that PttMAP20 has a role in cellulose biosynthesis. 相似文献
99.
Dichloromethane extracts of dried flowers of Calendula officinalis contain eight known bioactive triterpendiol monoesters, namely, faradiol-3-O-palmitate, faradiol-3-O-myristate, faradiol-3-O-laurate, arnidiol-3-O-palmitate, arnidiol-3-O-myristate, arnidiol-3-O-laurate, calenduladiol-3-O-palmitate and calenduladiol-3-O-myristate. These pentacyclic terpenoids have been quantified simultaneously using reversed-phase HPLC with isocratic elution and internal standardisation. Of the 10 varieties of C. officinalis investigated, Calypso Orange Florensis produced the highest amounts of the bioactive monoesters, followed by Fiesta Gitana Gelb and May Orange Florensis. The lipophilic extract from the flowers of Calypso Orange Florensis variety also contained low levels of the newly characterised calenduladiol-3-O-laurate. 相似文献
100.
Guerriero G Ferro R Russo GL Ciarcia G 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,138(4):435-439
This study reports titration of vitamin E levels in the sea bass (Dicentrarchus labrax) using high-pressure liquid chromatography. The first part of the work is devoted to vitamin E detection in: (1) plasma of maturing females and males characterized by different body sizes; (2) seminal fluid and eggs; and (3) developing embryos of sea bass fed with vitamin E. In the second part of the study, variations of vitamin E levels during larval development are analyzed. The results show a direct correlation between plasma vitamin E content and body size for both adult male and female sea bass. High vitamin E levels were found in seminal fluid, in eggs before and after fertilization, and in embryos during development and at hatching, whereas vitamin E level was low in dead embryos and in embryos with limited survival. During larval development, the vitamin E content decreased slowly but steadily during the first four days of larval growth; subsequently, it progressively increased from day 9 to day 40. In teratogenic larvae, vitamin E content was significantly higher than in normal larvae. This study provides evidence on how vitamin E exerts an antioxidant defense in sea bass reproduction. 相似文献