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81.
Yong-Tae Kim Deborah Downs Shili Wu Azar Dashti Yujun Pan Peng Zhai Xinjuan Wang Xuejun C Zhang Xinli Lin 《European journal of biochemistry》2002,269(22):5668-5677
BACE2 (Memapsin 1) is a membrane-bound aspartic protease that is highly homologous with BACE1 (Memapsin 2). While BACE1 processes the amyloid precursor protein (APP) at a key step in generating the beta-amyloid peptide and presumably causes Alzheimer's disease (AD), BACE2 has not been demonstrated to be directly involved in APP processing, and its physiological functions remain to be determined. In vivo, BACE2 is expressed as a precursor protein containing pre-, pro-, protease, transmembrane, and cytosolic domains/peptides. To determine the enzymatic properties of BACE2, two variants of its pro-protease domain, pro-BACE2-T1 (PB2-T1) and pro-BACE2-T2 (PB2-T2), were constructed. They have been expressed in Escherichia coli as inclusion bodies, refolded and purified. These two recombinant proteins have the same N terminus but differ at their C-terminal ends: PB2-T1 ends at Pro466, on the boundary of the postulated transmembrane domain, and PB2-T2 ends at Ser431, close to the homologous ends of other aspartic proteases such as pepsin. While PB2-T1 shares similar substrate specificities with BACE1 and other 'general' aspartic proteases, the specificity of PB2-T2 is more constrained, apparently preferring to cleave at the NH2-terminal side of paired basic residues. Unlike other 'typical' aspartic proteases, which are active only under acidic conditions, the recombinant BACE2, PB2-T1, was active at a broad pH range. In addition, pro-BACE2 can be processed at its in vivo maturation site by BACE1. 相似文献
82.
83.
Transdifferentiation of cardiac fibroblasts,a fetal factor in anti-SSA/Ro-SSB/La antibody-mediated congenital heart block 总被引:2,自引:0,他引:2
Clancy RM Askanase AD Kapur RP Chiopelas E Azar N Miranda-Carus ME Buyon JP 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(4):2156-2163
The signature lesion of autoantibody-associated congenital heart block (CHB) is fibrosis of the conducting tissue. To date, participation of myofibroblasts in the cascade to injury has been unexplored. The importance of myofibroblast/macrophage cross-talk is demonstrated by the novel finding of these cell types in the heart of a neonate dying of CHB. This clue to pathogenesis prompted consideration of the mechanism by which maternal anti-SSA/Ro-SSB/La Abs initiate an inflammatory response and promote fibrosis. Isolated cardiocytes from 16-24 wk abortuses were rendered apoptotic by exposure to poly (2-) hydroxyethylmethacrylate; flow cytometry confirmed surface expression of Ro/La. Apoptotic cardiocytes were incubated with affinity-purified Abs to 52 and 60 kDa Ro from CHB mothers (opsonized) or IgG fractions from healthy donors (nonopsonized). Macrophages cultured with opsonized apoptotic cardiocytes expressed proinflammatory markers, supported by a three-fold increase in active alpha(V)beta(3) integrin. Fetal cardiac fibroblasts exposed to supernatants obtained from macrophages incubated with opsonized apoptotic cardiocytes (but not nonopsonized) dramatically increased expression of the myofibroblast marker alpha-smooth muscle actin (SMAc). The "opsonized" supernatant reversed an inhibitory effect of the "nonopsonized" supernatant on proliferation of fibroblasts (120 vs 69%, p < 0.05). Parallel experiments examined the effects of two cytokines and their neutralizing Abs on fibroblasts. TGFbeta1 increased SMAc staining but decreased proliferation. TNF-alpha did not affect either readout. Addition of anti-TGFbeta1 Abs to the "opsonized" supernatant blocked SMAc expression but increased proliferation, while anti-TNF-alpha blocking Abs had no effects. These data suggest that transdifferentiation of cardiac fibroblasts to a scarring phenotype is a pathologic process initiated by maternal Abs. 相似文献
84.
85.
Background
Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals.Methods
Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration.Results
Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709).Conclusions
The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed. 相似文献86.
Excessive generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases, including
atherosclerosis, hypertension, and vascular complications of diabetes. However, the precise mechanisms by which ROS contribute
to the development of these diseases are not fully characterized. Hydrogen peroxide (H2O2), a ROS, has been shown to activate several signaling protein kinases, such as extracellular signal-regulated kinase (ERK)1/2
and protein kinase B (PKB) in different cell types, notably in vascular smooth muscle cells. Because these pathways regulate
cellular mitogenesis, migration, proliferation, survival, and death responses, their aberrant activtion has been suggested
to be a potential mechanism of ROS-induced pathologies. The upstream elements responsible for H2O2-induced ERK1/2 and PKB activation remain poorly characterized, but a potential role of receptor and nonreceptor protein tyrosine
kinases (PTKs) as triggers that initiate such events has been postulated. Therefore, the aim of this review is to highlight
the involvement of receptor and nonreceptor PTKs in modulating H2O2-induced ERK1/2 and PKB signaling. 相似文献
87.
Behzad Salehi Mansour Bayat Mehrouz Dezfulian Azar Sabokbar Bahman Tabaraie 《Saudi Journal of Biological Sciences》2018,25(6):1236-1241
Fungal polysaccharides are well-known for the medicinal properties such as antitumor and immunomodulating effects. Hence, this study evaluated antitumor effects of polysaccharide extracted from Fusarium sp. isolated from soil samples of Karaj district, Alborz, Iran along with its taxonomic study. The filamentous fungus strain FK1 was isolated from the soil sample of Karaj, Iran. The strain was identified based on cultural, morphological and 18 S rRNA gene parameters as Fusarium. Further, the strain Fusarium was cultured in fermented broth of modified (PDB) for 10 days at 25 °C. The polysaccharide of strain FK1 was extracted from the mycelium free supernatant by boiling water method and evaluated for antitoxicity effect on two human cancer cell lines: HeLa cell line and Lymphoblastoid cell line (LCL) by MTT method. Findings revealed that water-extracted from mycelia polysaccharide of strain FK1 had the highest cytotoxicity effect against LCL which is the cause of B lymphocyte cancer, at 50 μg/ml concentration dose (114 ± 1.63) followed by 100 μg/ml (105 ± 0.57) and 10 μg/ml (104 ± 0.57), while it did not have a considerable effect on HeLa cell line. Fusarium could be alternative sources as an antitumor component. 相似文献
88.
Mercury is one of the more common and potentially most harmful toxic metals. Remediation using conventional physical and chemical methods is uneconomical and generates large volumes of chemical waste. Bioremediation of hazardous metals has received considerable and growing interest over the years. In the present work, genetically engineered Escherichia coli cells, which express four rice metallothionein (MT) isoforms as fusions with glutathione-S-transferase (GST), were tested for their ability to remove mercury. The results showed that the E. coli cells expressing OsMT1, OsMT2, OsMT3, and OsMT4 are able to remove 20, 13.7, 10, and 7 nmol Hg2+/mg (dry weight) from the culture medium, respectively. The recombinant GST–OsMTs were purified using affinity chromatography. The UV absorption spectra and the results of 5,5-dithio-bis-(2-nitrobenzoic) acid (DTNB) assay recorded after the reconstitution of the apo-OsMTs with mercury confirmed that the different OsMT isoforms were able to form mercury complexes in vitro with different binding capacities and different binding strength. 相似文献
89.
Dany Azar ré Nel Michel Solignac Jean-Claude Paicheler & Françoise Bouchet 《Palaeontology》1999,42(6):1101-1136
Until now, only two Psychodoidea were known from Lebanese amber. We describe two new genera and species of Phlebotomidae ( Mesophlebotomites hennigi gen. et sp. nov., Libanophlebotomus lutfallahi gen. et sp. nov.) and four new genera with six new species of Psychodidae ( Paleopsychoda solignaci gen. et sp. nov., Paleopsychoda jacquelinae sp. nov., Protopsychoda nadiae gen. et sp. nov., Protopsychoda hammanaensis sp. nov., Libanopsychoda abillamai gen. et sp. nov., Cretapsychoda inexpectata gen. et sp. nov.) from the Lower Cretaceous amber of Hammana/Mdeirij, Lebanon. These fossils are included in a phylogenetic analysis of the subfamilies of Psychodoidea. This superfamily was probably as diverse in the Early Cretaceous as now. 相似文献
90.
There is considerable interest in the role of the TRK family of neuotrophin receptors in regulating growth and differentiation in normal and neoplastic nerve cells. A neuroblastoma is a common pediatric tumor derived from the neural crest, and the majority of favorable neuroblastomas express a high level of TRK-A mRNA. However, little is known about the expression or function of TRK-B in these tumors. TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the N-myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both TRK-B and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B as well as phosphorylation of phospholipase C-gamma 1, the extracellular signal-regulated kinases 1 and 2, and phosphatidylinositol-3 kinase. BDNF also induces expression of the immediate-early genes c-FOS and NGFI-A but not NGFI-B or NGFI-C. In addition, BDNF appears to promote cell survival and neurite outgrowth. SMS-KCN cells also express TRK-A, which is phosphorylated in response to nerve growth factor. However, the downstream TRK-A signaling is apparently defective. Finally, we determined that in a series of 74 primary neuroblastomas, 36% express TRK-B mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be preferentially expressed in more-differentiated tumors (ganglioneuromas and ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively in immature neuroblastomas with N-myc amplification. Our findings suggest that in TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be particularly important for growth and differentiation of neuroblastomas with N-myc amplification. 相似文献