全文获取类型
收费全文 | 117篇 |
免费 | 4篇 |
国内免费 | 3篇 |
专业分类
124篇 |
出版年
2013年 | 6篇 |
2012年 | 4篇 |
2011年 | 2篇 |
2010年 | 4篇 |
2009年 | 3篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 6篇 |
2005年 | 13篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
排序方式: 共有124条查询结果,搜索用时 15 毫秒
1.
N V Komissarova W E Siems O A Gomazkov P Oehme K D Jentzsch 《Biulleten' eksperimental'no? biologii i meditsiny》1982,93(6):3-5
Substance "P" (SP) and its derivatives inhibited activity of angiotensin-converting enzyme (ACE) in human blood serum, I50 for SP was 31 microM. The same results were obtained for N-terminal fragments of the SP molecule: Arg-Pro-Lys-Pro and Lys-Pro. The C-terminal heptapeptide and the dipeptide Arg-Pro negligibly inhibited ACE activity. A possible significance of the interaction between SP and ACE in the regulation of the microhemodynamics is discussed. 相似文献
2.
DC Chhieng AR Frost S Niwas H Weiss WE Grizzle S Beeken 《Biotechnic & histochemistry》2013,88(1):25-36
Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA. 相似文献
3.
C-type natriuretic peptide (CNP) is regarded as an endothelium-derived vasodilator and might therefore have an important role in controlling vascular tone and remodeling. Because CNP also is expressed in the brain, it is considered to be a neurotransmitter. The present study compares expression levels of CNP mRNA in distinct areas of the mouse brain with the expression pattern in the rat brain. A distinct expression of CNP was found in all investigated areas with the exception of the mouse striatum. In both rodents, high CNP expression was detected in the tegmentum. 相似文献
4.
The incorporation of 14C from [U-14C]adenine into the pools of purine nucleotides, nucleosides and bases in Ehrlich mouse ascites cells (EMAC1) during the proliferating and resting phases of tumor growth was compared. In the proliferating phase the total 14C incorporation into purine pools is much faster than in the resting phase. The ATP turnover as well as the purine breakdown to hypoxanthine and uric acid are increased in the proliferating phase. That corresponds to previous findings on higher nucleotide pool sizes and higher ATP yield and ATP-consuming processes in this growth period. 相似文献
5.
Sathyanarayanan PV Siems WF Jones JP Poovaiah BW 《The Journal of biological chemistry》2001,276(35):32940-32947
The existence of two molecular switches regulating plant chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK), namely the C-terminal visinin-like domain acting as Ca(2+)-sensitive molecular switch and calmodulin binding domain acting as Ca(2+)-stimulated autophosphorylation-sensitive molecular switch, has been described (Sathyanarayanan, P. V., Cremo, C. R., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 30417-30422). Here we report the identification of Ca(2+)-stimulated autophosphorylation site of CCaMK by matrix-assisted laser desorption ionization time of flight-mass spectrometry. Thr(267) was confirmed as the Ca(2+)-stimulated autophosphorylation site by post-source decay experiments and by site-directed mutagenesis. The purified T267A mutant form of CCaMK did not show Ca(2+)-stimulated autophosphorylation, autophosphorylation-dependent variable calmodulin affinity, or Ca(2+)/calmodulin stimulation of kinase activity. Sequence comparison of CCaMK from monocotyledonous plant (lily) and dicotyledonous plant (tobacco) suggests that the autophosphorylation site is conserved. This is the first identification of a phosphorylation site specifically responding to activation by second messenger system (Ca(2+) messenger system) in plants. Homology modeling of the kinase and calmodulin binding domain of CCaMK with the crystal structure of calcium/calmodulin-dependent protein kinase 1 suggests that the Ca(2+)-stimulated autophosphorylation site is located on the surface of the kinase and far from the catalytic site. Analysis of Ca(2+)-stimulated autophosphorylation with increasing concentration of CCaMK indicates the possibility that the Ca(2+)-stimulated phosphorylation occurs by an intermolecular mechanism. 相似文献
6.
H. Dautel O. Kahl K. Siems M. Oppenrieder L. Müller-Kuhrt M. Hilker 《Entomologia Experimentalis et Applicata》1999,91(3):431-441
A bioassay was developed to examine the response of ticks towards potential repellents that may protect vertebrates against tick bites. Such tick repellents must be effective despite the unavoidable presence of various attractive host-derived stimuli. Therefore, a moving-object-bioassay (MO-bioassay) was developed that mimicks body warmth and movement of vertebrates by a rotating and heated drum. Compounds which were tested for their effects on ticks were applied onto a small elevated area of the drum. Ticks were allowed to approach the drum by walking on a glass rod which ended 1 mm away from the local elevation. Ticks could cling to this elevation that intermittently passed by, whereas the remaining drum surface was too far away from the tip of the rod to be contacted by the ticks.Without the presence of any repellents, 85.5% of 600 hungry, field-collected Ixodes ricinus nymphs moved to the heated, rotating drum within 2 min. Further experiments with unfed I. ricinus nymphs were performed to test whether one established and two potential tick repellents elicit an avoidance reaction in the ticks despite the proven attractiveness of the drum. Freshly applied DEET (N,N-diethyl-m-toluamide) at a concentration of 0.11 mg cm–2 proved active as a repellent in the MO-bioassay over a distance of a few mm as well as by direct contact. A similar repellent effect was observed with (–)-myrtenal at 1 mg cm–2, but not at 0.1 mg cm–2, indicating that this terpenaldehyde is a weaker repellent for I. ricinus nymphs than DEET. No repellent effect was observed with camphor (0.1 mg cm–2).The MO-bioassay thus is a rapid, simple and low-cost test method allowing the investigation of tick host-contact behaviour as well as the screening of candidate repellents which are either perceived as volatiles or via contact chemoreception. 相似文献
7.
Siems W Capuozzo E Crifò C Sommerburg O Langhans CD Schlipalius L Wiswedel I Kraemer K Salerno C 《Biochimica et biophysica acta》2003,1639(1):27-33
Carotenoid supplementation in the treatment of diseases associated with oxidative stress has been recently questioned because of the cell damage and the increased risk of lung cancer in male smokers. Because of the complex role of neutrophils in lung diseases, we investigated whether carotenoid derivatives could affect respiratory burst and apoptosis of human neutrophils purified from peripheral blood. Stimulation of superoxide production was induced by nanomolar and micromolar concentrations of carotenoid cleavage products with aliphatic chains of different length, but not by carotenoids lacking the carbonyl moiety. The stimulatory effect of carotenoid cleavage products was observed in cells activated by phorbol myristate acetate (PMA), while a slight inhibition of superoxide production was noticed with cells activated by the chemotactic tripeptide N-formyl-Met-Leu-Phe (f-MLP). At higher concentrations, carotenoid cleavage products inhibited superoxide production in the presence of both PMA and f-MLP. In the presence of 20 microM carotenoid cleavage products, inhibition of superoxide production was accompanied by DNA fragmentation and increased level of intracellular caspase-3 activity. 相似文献
8.
Jenett-Siems K Kraft C Siems K Jakupovic J Solis PN Gupta MP Bienzle U 《Phytochemistry》2003,63(4):377-381
The phytochemical investigation of the leaves of Siparuna pauciflora yielded three novel sesquiterpenoids: the germacrane sipaucin A, the elemane sipaucin B and sipaucin C, comprising a new type of carbon skeleton. In addition, four known aporphine alkaloids-nor-boldine, boldine, laurotetanine, and N-methyl-laurotetanine-were obtained. The evaluation of the antiplasmodial activity of the isolated compounds against two strains of Plasmodium falciparum (PoW, Dd2) showed a moderate activity of nor-boldine. 相似文献
9.
4-hydroxynonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert a multitude of biological, cytotoxic, and signal effects. Mammalian cells possess highly active pathways of HNE metabolism. The metabolic fate of HNE was investigated in various mammalian cells and organs such as hepatocytes, intestinal enterocytes, renal tubular cells, aortic and brain endothelial cells, synovial fibroblasts, neutrophils, thymocytes, heart, and tumor cells. The experiments were carried out at 37 degrees C at initial HNE concentrations between 1 microM--that means in the range of physiological and pathophysiologically relevant HNE levels--to 100 microM. In all cell types which were investigated, 90-95% of 100 microM HNE were degraded within 3 min of incubation. At 1 microM HNE the physiological blood serum level of about 0.1-0.2 microM was restored already after 10-30 s. As primary products of HNE in hepatocytes and other cell types the glutathione-HNE-1:1-conjugate, the hydroxynonenoic acid and the corresponding alcohol of HNE, the 1,4-dihydroxynonene, were identified. Furthermore, the beta-oxidation of hydroxynonenoic acid including the formation of water was demonstrated. The quantitative share of HNE binding to proteins was low with about 2-8% of total HNE consumption. The glycine-cysteine-HNE, cysteine-HNE adducts and the mercapturic acid from glutathione-HNE adduct were not formed in the most cell types, but in kidney cells and neutrophils. The rapid metabolism underlines the role of HNE degrading pathways in mammalian cells as important part of the secondary antioxidative defense mechanisms in order to protect proteins from modification by aldehydic lipid peroxidation products. 相似文献
10.
Jenett-Siems K Ott SC Schimming T Siems K Müller F Hilker M Witte L Hartmann T Austin DF Eich E 《Phytochemistry》2005,66(2):223-231
A comprehensive GC-MS analysis of 8 Ipomoea species belonging to the subgenus Quamoclit, section Mina revealed that the members of this taxon form combinations of two necine bases with rare necic acids resulting in unique pyrrolizidine alkaloids. The occurrence and diversity of these metabolites show remarkable variations: Some species, especially Ipomoea hederifolia and Ipomoea lobata, are able to synthesize a large number of alkaloids whereas others, especially Ipomoea coccinea and Ipomoea quamoclit, are poor synthesizers with only a few compounds. However, these metabolites are apparently chemotaxonomic markers of this infrageneric taxon in general. They represent either esters of (-)-platynecine (altogether 48 ipangulines and 4 further esters including results of a previous study) or esters of (-)-trachelanthamidine, an additional novel structural type called minalobines (altogether 21 alkaloids). Both types are characterized by section-specific rare necic acids, e.g., ipangulinic/isoipangulinic acid, phenylacetic acid. The alkaloids of Ipomoea cholulensis, I. coccinea, I. hederifolia, Ipomoea neei, and Ipomoea quamoclit were mono and diesters of platynecine. Minalobines turned out to be metabolites of I. lobata (Cerv.) Thell. (syn.: Mina lobata Cerv.) lacking ipangulines. The major alkaloid of this species, minalobine R, has been isolated and identified as 9-O-(threo-2-hydroxy-2-methyl-3-phenylacetoxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data. Apparently only two of the species included in this study, Ipomoea cristulata and Ipomoea sloteri, are able to synthesize both, ipangulines as well as minalobines. Minalobine O could be isolated as a major alkaloid of I. cristulata, its structure has been established as 9-O-(erythro-2-hydroxy-2-methyl-3-tigloyloxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data. 相似文献