首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   64篇
  免费   9篇
  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 15 毫秒
31.
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.
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.
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  
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.
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.
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.
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   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号