全文获取类型
收费全文 | 118篇 |
免费 | 13篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 7篇 |
2013年 | 10篇 |
2012年 | 8篇 |
2011年 | 5篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有131条查询结果,搜索用时 15 毫秒
1.
Cecilia PC Soh Alastair SR Donald James Feeney Walter TJ Morgan Winifred M Watkins 《Glycoconjugate journal》1989,6(3):319-332
The tetrasaccharides GalNAcß1-4[NeuAc2-3]Galß1-4Glc and GalNAcß1-4[NeuAc2-3]Galß1-4GlcNAc were synthesised by enzymic transfer of GalNAc from UDP-GalNAc to 3-sialyllactose (NeuAc2-3Galß1-4Glc) and 3-sialyl-N-acetyllactosamine (NeuAc2-3Galß1-4GlcNAc). The structures of the products were established by methylation and1H-500 MHz NMR spectroscopy. In Sda serological tests the product formed with 3-sialyl-N-acetyllactosamine was highly active whereas that formed with 3-sialyllactose had only weak activity. 相似文献
2.
The morphology,innervation and neural control of the anterior arterial system of Aplysia californica
M. E. Skelton J. Koester 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1992,171(2):141-155
Summary The morphology, innervation, and neural control of the anterior arterial system of Aplysia californica were investigated. Immunocytochemical and histochemical techniques generated positive reactions in the anterior arterial system for several neuroactive substances, including SCPB, FMRFamide, R151 peptide, dopamine and serotonin. Three neurons were found to innervate the rostral portions of the anterior arterial tree. One is the identified peptidergic neuron R15 in the abdominal ganglion, and the other two are a pair of previously unidentified neurons, one in each pedal ganglion, named pedal arterial shorteners (PAS)- The endogeneously bursting neuron R15 was found to innervate the proximal anterior aorta. It also innervates a branch of the distal anterior aorta, the left pedal-parapodial artery. Activity in R15 causes constriction of the left pedal-parapodial artery. This effect is presumed to direct hemolymph towards the genital groove and penis on the right side in vivo. This vasoconstrictor action of R15 is mimicked by the R151 peptide. The PAS neuron pair causes longitudinal contraction of the rostral anterior aorta and the pedal-parapodial arteries. In vivo, the pair is active during behaviors involving head withdrawal and turning. By adjusting the length of the arteries during postural changes, the PAS neurons may prevent disturbances in blood flow due to bending or kinking of the arterial walls. 相似文献
3.
Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport 总被引:11,自引:9,他引:2 下载免费PDF全文
Catecholamines induce net salt and water movements in duck red cells incubated in isotonic solutions. The rate of this response is approximately three times greater than a comparable effect observed in 400 mosmol hypertonic solutions in the absence of hormone (W.F. Schmidt and T. J. McManus. 1977 a.J. Gen. Physiol. 70:59-79. Otherwise, these two systems share a great many similarities. In both cases, net water and salt movements have a marked dependence on external cation concentrations, are sensitive to furosemide and insensitive to ouabain, and allow the substitution of rubidium for external potassium. In the presence of ouabain, but the absence of external potassium (or rubidium), a furosemide-sensitive net extrusion of sodium against a large electrochemical gradient can be demonstrated. When norepinephrine-treated cells are incubated with ouabain and sufficient external sodium, the furosemide-sensitive, unidirectional influxes of both sodium and rubidium are half- maximally saturated at similar rubidium concentrations; with saturating external rubidium, the same fluxes are half-maximal at comparable levels of external sodium. In the absence of sodium, a catecholamine-stimulated, furosemide-sensitive influx of rubidium persists. In the absence of rubidium, a similar but smaller component of sodium influx can be seen. We interpret these results in terms of a cotransport model for sodium plus potassium which is activated by hypertonicity or norepinephrine. When either ion is absent from the incubation medium, the system promotes an exchange-diffusion type of movement of the co-ion into the cells. In the absence of external potassium, net movement of potassium out of the cell leads to a coupled extrusion of sodium against its electrochemical gradient. 相似文献
4.
The mRNA precursor encoded by the R15 gene is alternatively spliced in different neurons to form two related variants, R15-1 and R15-2 mRNA. One of the peptides encoded by the R15-2 mRNA, the R15 alpha 1 peptide, is expressed in the endogenously bursting neuron R15 and mediates some of its central and peripheral synaptic actions. In this study we found that the R15 alpha 2 peptide, which is encoded by the R15-1 mRNA, is synthesized in other neurons in the abdominal ganglion and is also bioactive. The R15 alpha 1 and R15 alpha 2 peptides were found to exert many similar actions on the cardiovascular, digestive, respiratory, and reproductive systems. However, the differences between many of the pharmacological effects of the R15 alpha 1 and R15 alpha 2 peptides indicate that alternative splicing in this system results in two functionally different peptides. Widespread immunoreactivity was found for an antibody directed against the R15 alpha 2 peptide, both in the central nervous system and the periphery. But because of the shared sequence with the R15 alpha 1 peptide, the antibody cross-reacts with the R15 alpha 1 peptide. To distinguish immunocytochemically between the two peptides, we also raised a second antibody that recognizes only the R15 alpha 1 peptide. This antibody labeled the cell body of only one neuron in the central nervous system, R15, although widespread immunoreactivity was found in axons and varicosities in the periphery. 相似文献
5.
6.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
7.
Alexei Kharitonenkov John M. Beals Radmila Micanovic Beth A. Strifler Radhakrishnan Rathnachalam Victor J. Wroblewski Shun Li Anja Koester Amy M. Ford Tamer Coskun James D. Dunbar Christine C. Cheng Christopher C. Frye Thomas F. Bumol David E. Moller 《PloS one》2013,8(3)
Fibroblast growth factor 21 is a novel hormonal regulator with the potential to treat a broad variety of metabolic abnormalities, such as type 2 diabetes, obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild type FGF21 (FGF21) has been shown to ameliorate metabolic disorders in rodents and non-human primates. However, development of FGF21 as a drug is challenging and requires re-engineering of its amino acid sequence to improve protein expression and formulation stability. Here we report the design and characterization of a novel FGF21 variant, LY2405319. To enable the development of a potential drug product with a once-daily dosing profile, in a preserved, multi-use formulation, an additional disulfide bond was introduced in FGF21 through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP), which was subject to proteolytic cleavage. In addition, to eliminate an O-linked glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing large-scale, homogenous protein production in Pichia pastoris. Altogether re-engineering of FGF21 led to significant improvements in its biopharmaceutical properties. The impact of these changes was assessed in a panel of in vitro and in vivo assays, which confirmed that biological properties of LY2405319 were essentially identical to FGF21. Specifically, subcutaneous administration of LY2405319 in ob/ob and diet-induced obese (DIO) mice over 7–14 days resulted in a 25–50% lowering of plasma glucose coupled with a 10–30% reduction in body weight. Thus, LY2405319 exhibited all the biopharmaceutical and biological properties required for initiation of a clinical program designed to test the hypothesis that administration of exogenous FGF21 would result in effects on disease-related metabolic parameters in humans. 相似文献
8.
9.
Hanselman JC Vartanian MA Koester BP Gray SA Essenburg AD Rea TJ Bisgaier CL Pape ME 《Molecular and cellular biochemistry》2001,217(1-2):91-97
Two alternatively spliced forms of human PPAR mRNA, PPAR1 and PPAR2, have been identified. PPAR1 mRNA gives rise to an active PPAR protein while PPAR2 mRNA gives rise to a form of PPAR which lacks the ligand-binding domain. PPAR2 is unable to activate a peroxisome proliferator response element (PPRE) reporter gene construct in transient transfection assays. Both PPAR1 and PPAR2 mRNA are present in human liver, kidney, testes, heart, small intestine, and smooth muscle. In human liver, PPAR2 mRNA abundance is approximately half that of PPAR1 mRNA; a correlation analysis of PPAR1 and PPAR2 mRNA mass revealed an r-value of 0.75 (n = 18). Additional studies with intact liver from various species, showed that the PPAR2/PPAR1 mRNA ratios in rat, rabbit, and mouse liver were less than 0.10; significantly lower than the 0.3 and 0.5 ratios observed in monkey and human livers, respectively. To determine if a high PPAR2/PPAR1 mRNA ratio was associated with insensitivity to peroxisome proliferators, we treated human, rat, and rabbit hepatocytes with WY14643, a potent PPARa activator, and measured acyl CoA oxidase (ACO) mRNA levels. Rat ACO mRNA levels increased markedly in response to WY14643 while human and rabbit hepatocytes were unresponsive. Thus, although the PPAR2/PPAR1 mRNA ratio is low in rabbits, this species is not responsive to peroxisome proliferators. Further studies with male and female rats, which vary significantly in their response to peroxisome proliferators, showed little difference in the ratio of PPAR2/PPAR1 mRNA. These data suggest that selective PPAR2 mRNA expression is not the basis for differential species or gender responses to peroxisome proliferators. 相似文献
10.
The diageotropica mutation alters auxin induction of a subset of the Aux/IAA gene family in tomato 总被引:5,自引:0,他引:5
The diageotropica (dgt) mutation has been proposed to affect either auxin perception or responsiveness in tomato plants. It has previously been demonstrated that the expression of one member of the Aux/IAA family of auxin-regulated genes is reduced in dgt plants. Here, we report the cloning of ten new members of the tomato Aux/IAA family by PCR amplification based on conserved protein domains. All of the gene family members except one (LeIAA7) are expressed in etiolated tomato seedlings, although they demonstrate tissue specificity (e.g. increased expression in hypocotyls vs. roots) within the seedling. The wild-type auxin-response characteristics of the expression of these tomato LeIAA genes are similar to those previously described for Aux/IAA family members in Arabidopsis. In dgt seedlings, auxin stimulation of gene expression was reduced in only a subset of LeIAA genes (LeIAA5, 8, 10, and 11), with the greatest reduction associated with those genes with the strongest wild-type response to auxin. The remaining LeIAA genes tested exhibited essentially the same induction levels in response to the hormone in both dgt and wild-type hypocotyls. These results confirm that dgt plants can perceive auxin and suggest that a specific step in early auxin signal transduction is disrupted by the dgt mutation. 相似文献