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排序方式: 共有111条查询结果,搜索用时 15 毫秒
71.
Matulenko MA Hakeem AA Kolasa T Nakane M Terranova MA Uchic ME Miller LN Chang R Donnelly-Roberts DL Namovic MT Moreland RB Brioni JD Stewart AO 《Bioorganic & medicinal chemistry》2004,12(13):3471-3483
Diaryl piperazine acetamides were identified as potent and selective dopamine D(4) receptor agonists. Our strategy is based on an amide bond reversal of an acid sensitive, dopamine D(4) receptor partial agonist, PD 168077. This reversal provided compounds with excellent potency and improved stability. Systematic evaluation of the substitution on the aryl piperazine portion revealed a significant effect on functional activity. The synthesis and biological activity of these new dopamine D(4) agonists is discussed. 相似文献
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Matulenko MA Surber B Fan L Kolasa T Nakane M Terranova MA Uchic ME Miller LN Chang R Donnelly-Roberts DL Namovic MT Moreland RB Brioni JD Stewart AO 《Bioorganic & medicinal chemistry letters》2004,14(20):5095-5098
The first selective dopamine D4 agonist radioligand is described. The synthesis of these piperazine radioligands relied on the transformation of brominated precursors 4a and 4b with tritium gas in the presence of a sensitive cyano functional group. The specific activity of these two radioligands was measured and [3H]6b found to be suitable for use in D4 saturation and competition binding studies. The synthesis, biological, and radioactivity of this new agonist radioligand as well as preliminary SAR will be discussed. 相似文献
74.
Transmembrane redox control and proteolysis of PdeC,a novel type of c‐di‐GMP phosphodiesterase
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Susanne Herbst Martin Lorkowski Olga Sarenko Thi Kim Loan Nguyen Tina Jaenicke Regine Hengge 《The EMBO journal》2018,37(8)
The nucleotide second messenger c‐di‐GMP nearly ubiquitously promotes bacterial biofilm formation, with enzymes that synthesize and degrade c‐di‐GMP being controlled by diverse N‐terminal sensor domains. Here, we describe a novel class of widely occurring c‐di‐GMP phosphodiesterases (PDE) that feature a periplasmic “CSS domain” with two highly conserved cysteines that is flanked by two transmembrane regions (TM1 and TM2) and followed by a cytoplasmic EAL domain with PDE activity. Using PdeC, one of the five CSS domain PDEs of Escherichia coli K‐12, we show that DsbA/DsbB‐promoted disulfide bond formation in the CSS domain reduces PDE activity. By contrast, the free thiol form is enzymatically highly active, with the TM2 region promoting dimerization. Moreover, this form is processed by periplasmic proteases DegP and DegQ, yielding a highly active TM2 + EAL fragment that is slowly removed by further proteolysis. Similar redox control and proteolysis was also observed for a second CSS domain PDE, PdeB. At the physiological level, CSS domain PDEs modulate production and supracellular architecture of extracellular matrix polymers in the deeper layers of mature E. coli biofilms. 相似文献
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Microctonus hyperodae Loan, new species, is a parasite of adults of the stem weevilHyperodes bonariensis Kuschel in Argentina and Uruguay. It is described and identification characters are given for the three other known Neotropical species ofMicroctonus. The life cycle, incidence and control importance ofM. hyperodae are reported. 相似文献
77.
P. Loan Honeywell-Nguyen H. W. Wouter Groenink Joke A. Bouwstra 《Journal of liposome research》2013,23(3):273-280
The main problem in delivery of drugs across the skin is the barrier function of the skin, which is located in the outermost layer of the skin, the stratum corneum. The stratum corneum consists of corneocytes surrounded by lipid layers, the so-called lipid lamellae. When applying drugs onto the skin, the major penetration pathway is the tortuous intercellular route along the lipid lamellae. In order to increase the number of drugs administered via the transdermal route, novel drug delivery systems have to be designed. Among these systems are iontophoresis, electroporation, microneedles, and vesicular systems. 相似文献
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Thirteen analgesic drugs, four of them at two dose levels, four analgesics in combination with antagonist or neuroleptic agents, and saline have been evaluated simultaneously in the relief of postoperative pain. The method of assessment was designed to favour drugs which provided freedom from pain with minimum depression of consciousness. Only levorphanol 2 mg proved significantly superior to pethidine 100 mg, which was used as the standard reference drug. Oxycodone 10 mg, pentazocine 20 mg, and the morphine 10 mg and cyclizine 50 mg combination were the most successful of the remaining drugs. None of the drug combinations was significantly better than the analgesic drug given alone. 相似文献
80.
Phan LK Chung WK Leibel RL 《American journal of physiology. Endocrinology and metabolism》2006,291(3):E611-E620
Mahoganoid (Mgrn1(md)) is a mutation of the mahogunin (Mgrn1) gene. The hypomorphic allele suppresses the yellow pigmentation and obesity of the A(y) mouse that ubiquitously overexpresses agouti signaling protein (ASP). To assess the physiological effects of MGRN1 on energy and glucose homeostasis, we generated animals doubly mutant for Mgrn1(md) and A(y), Lep(ob), or a null allele of Mc4r, and diet-induced obesity (DIO) mice segregating for Mgrn1(md). Mgrn1(md) suppressed the obesity, hyperglycemia, and hyperinsulinemia of A(y) mice. Mgrn1(md) suppressed A(y)-induced obesity by reducing food intake, and reduced adiposity in Lep(ob)/Lep(ob) females, but did not alter the body weight or body composition of mice fed a high-fat diet. There was no effect of Mgrn1(md) on weight gain, body composition, energy intake, or energy expenditure in Mc4r-null animals. Mgrn1(md) reduced circulating insulin concentrations in DIO, A(y), and Mc4r-null but not Lep(ob)/Lep(ob) mice. The effect of Mgrn1(md) on circulating insulin concentrations was not due primarily to reductions in fat mass, since the plasma insulin concentrations of Mgrn1(md) mice segregating for either A(y) or Mc4r-null alleles, adjusted for fat mass and plasma glucose, were reduced compared with A(y) and Mc4r mice, respectively. The effect of Mgrn1(md) on insulin sensitivity of Mc4r-null mice suggests that Mgrn1(md) may be increasing insulin sensitivity via the hypothalamic melanocortin-3 receptor pathway. 相似文献