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61.
Human emotions are strongly shaped by the tendency to compare the relative state of oneself to others. Although social comparison based emotions such as jealousy and schadenfreude (pleasure in the other misfortune) are important social emotions, little is known about their developmental origins. To examine if schadenfreude develops as a response to inequity aversion, we assessed the reactions of children to the termination of unequal and equal triadic situations. We demonstrate that children as early as 24 months show signs of schadenfreude following the termination of an unequal situation. Although both conditions involved the same amount of gains, the children displayed greater positive expressions following the disruption of the unequal as compared to the equal condition, indicating that inequity aversion can be observed earlier than reported before. These results support an early evolutionary origin of inequity aversion and indicate that schadenfreude has evolved as a response to unfairness. 相似文献
62.
Laurent D Jullian V Parenty A Knibiehler M Dorin D Schmitt S Lozach O Lebouvier N Frostin M Alby F Maurel S Doerig C Meijer L Sauvain M 《Bioorganic & medicinal chemistry》2006,14(13):4477-4482
As part of our search for new antimalarial drugs, we have screened for inhibitors of Pfnek-1, a protein kinase of Plasmodium falciparum, in south Pacific marine sponges. On the basis of a preliminary screening, the ethanolic crude extract of a new species of Xestospongia collected in Vanuatu was selected for its promising activity. A bioassay-guided fractionation led us to isolate xestoquinone which inhibits Pfnek-1 with an IC(50) around 1 microM. Among a small panel of plasmodial protein kinases, xestoquinone showed modest protein kinase inhibitory activity toward PfPK5 and no activity toward PfPK7 and PfGSK-3. Xestoquinone showed in vitro antiplasmodial activity against a FCB1 P. falciparum strain with an IC(50) of 3 microM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses. 相似文献
63.
Janetka JW Almeida L Ashwell S Brassil PJ Daly K Deng C Gero T Glynn RE Horn CL Ioannidis S Lyne P Newcombe NJ Oza VB Pass M Springer SK Su M Toader D Vasbinder MM Yu D Yu Y Zabludoff SD 《Bioorganic & medicinal chemistry letters》2008,18(14):4242-4248
Checkpoint kinase-1 (Chk1, CHEK1) is a Ser/Thr protein kinase that mediates the cellular response to DNA-damage. A novel class of 2-ureido thiophene carboxamide urea (TCU) Chk1 inhibitors is described. Inhibitors in this chemotype were optimized for cellular potency and selectivity over Cdk1. 相似文献
64.
Submucosal glands (SMG) are important secretory glands that are present in the major airways and bronchioles of humans. In
mice the structure, cellular composition, and density of SMG are similar to those seen in humans, but the glands are present
only in the trachea. Characterization of SMG is important as they secrete bacteriocidal products such as lactoferrin, lysozyme,
and defensins believed to be of importance in the innate defense system. Serous cells in SMG are the primary site of cystic
fibrosis transmembrane conductance regulator (CFTR) gene expression and the initial site of histological abnormality in cystic
fibrosis (CF) individuals. In this study, we examined four inbred strains of mice (A/J, C57BL/6N, FVB/N, and BALB/CAnN) and
revealed that the extent to which glands descend in the mouse trachea varied between inbred strains. In particular, the A/J
and C57BL/6N strains exhibited few SMG extending further than the first or second intercartilaginous space (mean depth of
0.4 ± 0.11 and 1.5 ± 0.32 tracheal rings respectively) in the trachea, whereas the FVB/N and BALB/CAnN strains had SMG extending
beyond the fourth space (mean depths of 3.3 ± 0.46 and 5.6 ± 0.45 rings respectively). We have previously shown that in congenic
C57Bl/6N Cftr mutant mice (CF mice), the SMG are distributed more distally than in wild-type C57Bl/6N but are indistinguishable from BALB/CAnN
wild-type or CF mice. The implication that SMG distribution is influenced by Cftr gene expression (or a gene closely linked to Cftr) led us to investigate the genetic difference between C57Bl6/N and BALB/CAnN mice. In recombinant inbred strain (RIS) analysis
(with BALB/CJ and C57BL/6J progenitors), two loci were identified as being linked to the SMG phenotype (peak likelihood statistic
levels of 8.8 and 9.9 on Chrs 9 and 10 respectively, indicating suggestive linkage). A subsequent segregation analysis of
an F2 intercross between the C57BL/6N and BALB/CAnN mice indicated that there were at least two major genetic factors responsible
for SMG distribution. The loci indicated in the RI analysis were included in a targeted genome scan involving 235 F2 intercross animals (C57BL/6N and BALB/CAnN strain intercross). The genome scan confirmed the locus on Chr 9 (between genetic
markers D9Mit11 and D9Mit182), designated Smgd1, as significantly linked to the SMG distribution phenotype (peak LOD score 5.8) within a 95% confidence interval of 12 cM.
Received: 26 June 2000 / Accepted: 18 September 2000 相似文献
65.
Nayeli Goreti Nieto-Velázquez Yessica Dorin Torres-Ramos José Luis Mu?oz-Sánchez Lorena Espinosa-Godoy Susana Gómez-Cortés José Moreno Mario Adán Moreno-Eutimio 《Translational oncology》2016,9(5):384-391
Human natural killer (NK) cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy), 10 benign breast pathology patients, and 24 control individuals. CD3−CD56dimCD16bright NK cells (CD56dim NK) and CD3−CD56brightCD16dim/− NK cells (CD56bright NK) were identified using flow cytometry. The circulating counts of CD56dim and CD56bright NK cells were not significantly different between the groups evaluated, nor were the counts of other leukocyte subsets between the breast cancer patients and benign breast pathology patients. However, in CD56dim NK cells, NKp44 expression was higher in breast cancer patients (P = .0302), whereas NKp30 (P = .0005), NKp46 (P = .0298), and NKG2D (P = .0005) expression was lower with respect to healthy donors. In CD56bright NK cells, NKp30 (P = .0007), NKp46 (P = .0012), and NKG2D (P = .0069) expression was lower in breast cancer patients compared with control group. Only NKG2D in CD56bright NK cells (P = .0208) and CD56dim NK cells (P = .0439) showed difference between benign breast pathology and breast cancer patients. Collectively, the current study showed phenotypic alterations in activation receptors on CD56dim and CD56bright NK cells, suggesting that breast cancer patients have decreased NK cell cytotoxicity. 相似文献
66.
67.
Netanel Tzarum Nadav Komornik Dorin Ben Chetrit David Engelberg Oded Livnah 《The Journal of biological chemistry》2013,288(27):19537-19547
Signaling processes are primarily promoted by molecular recognition and corresponding protein-protein interactions. One of the key eukaryotic signaling pathways is the MAP kinase cascade involved in vital cellular processes such as cell proliferation, differentiation, apoptosis, and stress response. The principle recognition site of MAP kinases, the common docking (CD) region, forms selective interactions with substrates, upstream activators, and phosphatases. A second docking site, defined as the DEF site interaction pocket (DEF pocket), is formed subsequent to ERK2 and p38α activation. Both crystal structures of p38α in its dually phosphorylated form and of intrinsically active mutants showed the DEF pocket, giving motivation for studying its role in substrate activation and selectivity. Mutating selected DEF pocket residues significantly decreased the phosphorylation levels of three p38α substrates (ATFII, Elk-1, and MBP) with no apparent effect on the phosphorylation of MK2 kinase. Conversely, mutating the CD region gave the opposite effect, suggesting p38α substrates can be classified into DEF-dependent and DEF-independent substrates. In addition, mutating DEF pocket residues decreased the autophosphorylation capability of intrinsically active p38α mutants, suggesting DEF-mediated trans-autophosphorylation in p38α. These results could contribute to understanding substrate selectivity of p38α and serve as a platform for designing p38α-selective DEF site blockers, which partially inhibit p38α binding DEF-dependent substrates, whereas maintaining its other functions intact. In this context, preliminary results using synthetic peptides reveal significant inhibition of substrate phosphorylation by activated p38α. 相似文献
68.
69.
M. Shrestha M. Burd J. E. Garcia A. Dorin A. G. Dyer 《Plant biology (Stuttgart, Germany)》2019,21(4):745-752
- Orchids are a classic angiosperm model for understanding biotic pollination. We studied orchid species within two species‐rich herbaceous communities that are known to have either hymenopteran or dipteran insects as the dominant pollinators, in order to understand how flower colour relates to pollinator visual systems.
- We analysed features of the floral reflectance spectra that are significant to pollinator visual systems and used models of dipteran and hymenopteran colour vision to characterise the chromatic signals used by fly‐pollinated and bee‐pollinated orchid species.
- In contrast to bee‐pollinated flowers, fly‐pollinated flowers had distinctive points of rapid reflectance change at long wavelengths and a complete absence of such spectral features at short wavelengths. Fly‐pollinated flowers also had significantly more restricted loci than bee‐pollinated flowers in colour space models of fly and bee vision alike.
- Globally, bee‐pollinated flowers are known to have distinctive, consistent colour signals. Our findings of different signals for fly pollination is consistent with pollinator‐mediated selection on orchid species that results from the distinctive features of fly visual systems.
70.