全文获取类型
收费全文 | 64篇 |
免费 | 9篇 |
出版年
2022年 | 3篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 1篇 |
2013年 | 1篇 |
2012年 | 2篇 |
2011年 | 5篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1976年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有73条查询结果,搜索用时 38 毫秒
31.
Zificsak CA Theroff JP Aimone LD Albom MS Angeles TS Brown RA Galinis D Grobelny JV Herbertz T Husten J Kocsis LS LoSardo C Miknyoczki SJ Murthy S Rolon-Steele D Underiner TL Wells-Knecht KJ Worrell CS Zeigler KS Dorsey BD 《Bioorganic & medicinal chemistry letters》2011,21(2):660-663
Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response. 相似文献
32.
J. Jeffry Howbert Edward E. Patterson S. Matt Stead Ben Brinkmann Vincent Vasoli Daniel Crepeau Charles H. Vite Beverly Sturges Vanessa Ruedebusch Jaideep Mavoori Kent Leyde W. Douglas Sheffield Brian Litt Gregory A. Worrell 《PloS one》2014,9(1)
Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. 相似文献
33.
34.
35.
Bryostatin-1 enhances barrier function in T84 epithelia through PKC-dependent regulation of tight junction proteins 总被引:4,自引:0,他引:4
Yoo J Nichols A Mammen J Calvo I Song JC Worrell RT Matlin K Matthews JB 《American journal of physiology. Cell physiology》2003,285(2):C300-C309
Protein kinase C (PKC) is known to regulate epithelial barrier function. However, the effect of specific PKC isozymes, and their mechanism of action, are largely unknown. We determined that the nonphorbol ester PKC agonist bryostatin-1 increased transepithelial electrical resistance (TER), a marker of barrier function, in confluent T84 epithelia. Bryostatin-1, which has been shown to selectively activate PKC-, -, and - (34), was associated with a shift in the subcellular distribution of the tight junction proteins claudin-1 and ZO-2 from a detergent-soluble fraction into a detergent-insoluble fraction. Bryostatin-1 also led to the appearance of a higher-molecular-weight form of occludin previously shown to correspond to protein phosphorylation. These changes were attenuated by the conventional and novel PKC inhibitor Gö-6850 but not the conventional PKC inhibitor Gö-6976 or the PKC- inhibitor röttlerin, implicating a novel isozyme, likely PKC-. The results suggest that enhanced epithelial barrier function induced by bryostatin-1 involves a PKC--dependent signaling pathway leading to recruitment of claudin-1 and ZO-2, and phosphorylation of occludin, into the tight junctional complex. protein kinase C; epithelial barrier function 相似文献
36.
Effects of fatty acids on BK channels in GH(3) cells 总被引:6,自引:0,他引:6
Denson DD Wang X Worrell RT Eaton DC 《American journal of physiology. Cell physiology》2000,279(4):C1211-C1219
Ca2+-activated K+ (BK) channels inGH3 cells are activated by arachidonic acid (AA). Becausecytosolic phospholipase A2 can produce other unsaturatedfree fatty acids (FFA), we examined the effects of FFA on BK channelsin excised patches. Control recordings were made at several holdingpotentials. The desired FFA was added to the bath solution, and thevoltage paradigm was repeated. AA increased the activity of BK channelsby 3.6 ± 1.6-fold. The cis FFA, palmitoleic, oleic,linoleic, linolenic, eicosapentaenoic, and the triple bond analog ofAA, eicosatetraynoic acid, all increased BK channel activity, whereasstearic (saturated) or the trans isomers elaidic,linolelaidic, and linolenelaidic had no effect. The cisunsaturated FFA shifted the open probability vs. voltage relationshipsto the left without a change in slope, suggesting no change in thesensitivity of the voltage sensor. Measurements of membrane fluidityshowed no correlation between the change of membrane fluidity and thechange in BK channel activation. In addition, AA effects on BK channelswere unaffected in the presence of N-acetylcysteine.Arachidonyl-CoA, a membrane impermeable analog of AA, activateschannels when applied to the cytosolic surface of excised patches,suggesting an effect of FFAs from the cytosolic surface of BK channels.Our data imply a direct interaction between cis FFA and theBK channel protein. 相似文献
37.
Meat,dairy, and more: Analysis of material,energy, and greenhouse gas flows of the meat and dairy supply chains in the EU28 for 2016 总被引:1,自引:0,他引:1
Stephen Ivan aan den Toorn Ernst Worrell Machteld A. van den Broek 《Journal of Industrial Ecology》2020,24(3):601-614
To decarbonize the European Union, protein consumption must transition to diets low in meat and dairy which will drastically change the material and energy flows in current meat and dairy supply chains. To understand the impacts on current flows, a baseline is required. Although recent studies have improved the scope of reported greenhouse gas (GHG) emissions, no quantitative overview exists including intermediate and final product flows. To address this knowledge gap, we structured the meat and dairy supply chains into a connected set of transformation nodes and distribution nodes. The former are processes transforming inputs into outputs, whereas the latter distribute the outputs to other processes using them as inputs. Currently, livestock play a central role in agriculture and other industries through the consumption of 271 Mt fodder crops, 108 Mt grain, 85 Mt grazed biomass, 49 Mt oil meal, and 16 Mt feed by‐products. This feed is transformed into 64 Mt dairy and 35 Mt meat which ensures that the EU28 is a net exporter of meat and dairy while providing 25 Mt of by‐products. This production also leads to 435 Mt CO2‐eq. with the main contribution from beef cattle (35%), dairy cattle (32%), and swine (20%). Thus, the lower GHG intensities of dairy products compared to meat do not imply a low contribution to the total emissions. By mapping the material, energy, and GHG emission flows, we have created a baseline suitable for identifying potential supply chain changes and their related GHG increase or decrease resulting from the protein transition. 相似文献
38.
39.
Worrell C Xiao N Vidal JE Chen L Zhong B Remais J 《Applied and environmental microbiology》2011,77(6):2192-2195
A species-specific quantitative PCR (qPCR) assay was combined with two novel water-sampling methods and compared with the mouse bioassay for the quantitative detection of S. japonicum in surface waters. The novel methods were capable of capturing cercariae and, with subsequent analysis through qPCR, detecting the presence of a minimum of 1 cercaria. 相似文献
40.
Milkiewicz KL Aimone LD Albom MS Angeles TS Chang H Grobelny JV Husten J Losardo C Miknyoczki S Murthy S Rolon-Steele D Underiner TL Weinberg LR Worrell CS Zeigler KS Dorsey BD 《Bioorganic & medicinal chemistry》2011,19(21):6274-6284
The hepatocyte growth factor (HGF)-c-Met signaling axis is involved in the mediation of many biological activities, including angiogenesis, proliferation, cell survival, cell motility, and morphogenesis. Dysregulation of c-Met signaling (e.g., overexpression or increased activation) is associated with the proliferation and metastasis of a wide range of tumor types, including breast, liver, lung, colorectal, gastric, bladder, and prostate, among others. Inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which pharmaceutical properties were modulated by substituents appended on the C2-benzazepinone ring. In particular, certain-3-amidobenzazepin-2-one analogs had improved oral bioavailability and were evaluated in PK/PD and efficacy models. Lead compounds demonstrated tumor stasis with partial regressions when evaluated in a GTL-16 tumor xenograft mouse model. 相似文献