全文获取类型
收费全文 | 266篇 |
免费 | 17篇 |
专业分类
283篇 |
出版年
2023年 | 3篇 |
2021年 | 9篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 10篇 |
2013年 | 10篇 |
2012年 | 6篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 4篇 |
2008年 | 3篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 11篇 |
2002年 | 8篇 |
2001年 | 10篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 11篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1968年 | 4篇 |
1967年 | 2篇 |
1963年 | 2篇 |
排序方式: 共有283条查询结果,搜索用时 15 毫秒
1.
Mandip Singh Gary Faulkner Tarun I. Ghose Michael Mezei 《Cancer immunology, immunotherapy : CII》1988,27(1):17-25
Summary The potential of antibody-linked SUVs containing MTX in anticancer therapy was investigated. The SUVs, mean diameter 50±20 nm, were prepared by probe sonication of MTX-containing MLVs and were covalently linked either to a RAMG or NRG. After incubation with M21 melanoma cells for 2 h, RAMG-linked SUVs showed 2 and 4 times more binding than NRG-linked MTX-containing SUVs or MTX-containing SUVs unlinked to any Ig. Furthermore, on incubating M21 melanoma cells with RAMG-linked 3H MTX-containing SUVs for 2, 4, and 8 h at 4° C or 37° C, a higher radioactivity was associated with cells at 37° C than at 4° C. Membrane immunofluorescence revealed aggregation of and cap formation by RAMG-linked SUVs after 2 h (37° C) and endocytosis at 4 and 8 h at 37° C. Electron microscopic and autoradiographic studies confirmed aggregation of 3H MTX-containing SUVs around and on the surface of M21 cells. Electron microscopy also revealed these SUVs inside invaginations of and under the plasma membrane of melanoma cells. A colony inhibition assay showed that RAMG-linked, MTX-containing SUVs were 60 times, 8 times, and 4.5 times more growth inhibitory than free MTX, NRG-linked MTX-containing SUV, and MTX-containing SUVs unlinked to any Ig, but not toxic to a human kidney cancer line (that did not react with RAMG).
Abbreviations used: DPPC, DL- -dipalmitoyl phosphatidylcholine; DTT, dithiothreitol; MTX, methotrexate; (MTX)SUV or MLV, MTX-containing SUV or MLV; MLV, multilamellar vesicle; NRG, normal rabbit immunoglobulin G; RAMG, rabbit antimelanoma IgG; SA, stearylamine; SPDP, N-succinimidy1-3-(2-pyridyldithio)propionate; SUV, small unilamellar vesicle; CHOL, cholesterol; LUV, large unilamellar vesicle; Ig, immunoglobulin; PDP-SA, N-[3-(2-pyridyldithio)-propinyl]stearylamine 相似文献
2.
Laboratory examination of specimens from 123 consecutive renal biopsies performed at Victoria General Hospital, Halifax revealed six cases of mesangial deposition, predominantly of IgA, unassociated with systemic disorders. Immunohistologic examination showed deposits of only IgA in one specimen, IgA and IgG in two and IgA, IgG and IgM in three. Glomerular deposits of C3 were seen in five of the specimens, and properdin was seen in three. Glomeruli in all the specimens showed increased matrix and increased numbers of cells in the mesangium. Electron microscopy revealed deposits in the mesangium or capillary wall in all five of the specimens so studied. All six patients had proteinuria, four had microscopic hematuria, and three had hypertension; in one patient the disease progressed to renal failure. 相似文献
3.
Epidemic isolates of Vibrio cholerae 0139 express antigenically distinct types of colonization pili 总被引:2,自引:0,他引:2
T.K. Sengupta D.K. Sengupta G. Balakrish Nair Asoke C. Ghose 《FEMS microbiology letters》1994,118(3):265-271
Abstract Vibrio cholerae belonging to the recently described serogroup 0139, which are responsible for the current cholera epidemics in India and Bangladesh, were shown to express pilus-like structures partially cross-reacting with the toxin-coregulated pilus of V. cholerae strain (0395) belonging to the 01 serogroup and classical biotype. The 0139 pili were composed of 20 kDa subunit proteins which were antigenically related to the 20 kDa pilus protein of another diarrhoeagenic non-01 V. cholerae strain (serogroup 034) isolated earlier. The pili described in this study were found to be involved in the intestinal colonization process and, therefore, may contribute towards the virulence of the 0139 epidemic isolates. 相似文献
4.
D. M. Lonsdale R. L. Allen D. Belostotsky T. K. Ghose A. J. Harvey H. J. Rogers S. J. Tebbut M. Trick 《Plant cell reports》1995,15(1-2):154-158
Summary The promoters of a tobacco actin gene, a tobacco pectate lyase, a tobacco and maize polygalacturonase and aBrassica S-locus related gene have been fused to the-glucuronidase reporter gene and their activities determined by biolistic transient assay in tobacco pollen. In stably transformed tobacco all the transgenes with the exception of Cauliflower Mosaic Virus-35S--glucuronidase appear to express efficiently in maturing pollen. Transient assay analysis showed that the tobacco pectate lyase and the polygalacturonase constructs were 8x more active than the tobacco actin construct, and that the tobacco polygalacturonase construct was some 33x more active than the maize polygalacturonase construct. Constructional manipulations that altered the lengths of the 5-untranslated leaders including one which resulted in the removal of a 490 bp leader intron had little effect on the observed level of expression. However, the alteration of the context of the ATG from A/TnnATGG to CnnATGT resulting in a 70% reduction in the observed levels of activity, was obtained with the pectate lyase and polygalacturonase promoters. An identical reductional was also observed in transgenic plant populations transformed with the polygalacturonase transgenes.Abbreviations GUS
-glucuronidase
- LUC
luciferase
- NosTer
nopaline synthase terminator
- CaMV
Cauliflower Mosaic Virus
- UTL
untranslated leader
- PCR
polymerase chain reaction
- PG
polygalacturonase
- Npg
tobacco polygalacturonase
- Pl
pectate lyase
- Ac
actin 相似文献
5.
We studied the response of 31 migraine sufferers (20 women, 11 men) to intravenous tyramine (the tyraminedose)pressor response test). Patients were treated either with pacebo tablets or indoramin, and alpha-adrenergic blocking agent, in a double-blind crrossover trial. We found that patients with migraine required significantly less tyramine to increase their cystolic blod pressure by 30 mm Hg when compared with matched controls. Indoramin significantly increased the amount of tyramine needed to raise the systolic blood pressure among migraine suffers and reduced the incidence of posttyramine migraine for m 46% while patients were on placebo tablets to 8% when they were receiveing indoramin. There was no association between tyramine sensitivity and a history of premenstrual or dietary migraine, nor was there a significant difference in the indierenence in the incidence of post-tyramine migrain between men women. We conclude that the intravenous tyramine test may be valuable in assessing migraine suffers who will respond to an alpha-advenergic blocking agent such as indoramin. 相似文献
6.
7.
Batch and single-flow four-stage continuous ethanol fermentations of bagasse hydrolysate have been investigated at pH 4.0 and 30°C with a strain of the yeast Saccharomyces cerevisiae. The studies were carried out in the laboratory four-stage cascade continuous stirred-tank fermentors at varying feed glucose concentrations (10, 14, 18, and 22%). The range of dilution rates employed varied from 0.05 to 0.2 hr?1. The hydrolysate was supplemented with a cheap nitrogen source (CNS), CaCl2·H2O and MgSO4·7H2O. A 2% (v/v) CNS concentration was found to be sufficient to avoid growth limitation at a glucose concentration of 116 g/liter. The conditions of continuous culture in a multistage system are predicted by a graphical method based on batch-culture data. The results thus obtained are compared with those predicted by kinetic models and with the experimental results. The variations between the results obtained experimentally and those computed either by a kinetic model or by graphical analyses were found to be within the limits of experimental error. The solutions based on the concept of minimum residence time necessary to achieve the desired biomass or product concentrations are also discussed. 相似文献
8.
9.
10.
Matthew J. Cooper Nathan J. Cox Eric I. Zimmerman Brian J. Dewar James S. Duncan Martin C. Whittle Thien A. Nguyen Lauren S. Jones Sreerupa Ghose Roy David M. Smalley Pei Fen Kuan Kristy L. Richards Richard I. Christopherson Jian Jin Stephen V. Frye Gary L. Johnson Albert S. Baldwin Lee M. Graves 《PloS one》2013,8(6)
Protein kinases play key roles in oncogenic signaling and are a major focus in the development of targeted cancer therapies. Imatinib, a BCR-Abl tyrosine kinase inhibitor, is a successful front-line treatment for chronic myelogenous leukemia (CML). However, resistance to imatinib may be acquired by BCR-Abl mutations or hyperactivation of Src family kinases such as Lyn. We have used multiplexed kinase inhibitor beads (MIBs) and quantitative mass spectrometry (MS) to compare kinase expression and activity in an imatinib-resistant (MYL-R) and -sensitive (MYL) cell model of CML. Using MIB/MS, expression and activity changes of over 150 kinases were quantitatively measured from various protein kinase families. Statistical analysis of experimental replicates assigned significance to 35 of these kinases, referred to as the MYL-R kinome profile. MIB/MS and immunoblotting confirmed the over-expression and activation of Lyn in MYL-R cells and identified additional kinases with increased (MEK, ERK, IKKα, PKCβ, NEK9) or decreased (Abl, Kit, JNK, ATM, Yes) abundance or activity. Inhibiting Lyn with dasatinib or by shRNA-mediated knockdown reduced the phosphorylation of MEK and IKKα. Because MYL-R cells showed elevated NF-κB signaling relative to MYL cells, as demonstrated by increased IκBα and IL-6 mRNA expression, we tested the effects of an IKK inhibitor (BAY 65-1942). MIB/MS and immunoblotting revealed that BAY 65-1942 increased MEK/ERK signaling and that this increase was prevented by co-treatment with a MEK inhibitor (AZD6244). Furthermore, the combined inhibition of MEK and IKKα resulted in reduced IL-6 mRNA expression, synergistic loss of cell viability and increased apoptosis. Thus, MIB/MS analysis identified MEK and IKKα as important downstream targets of Lyn, suggesting that co-targeting these kinases may provide a unique strategy to inhibit Lyn-dependent imatinib-resistant CML. These results demonstrate the utility of MIB/MS as a tool to identify dysregulated kinases and to interrogate kinome dynamics as cells respond to targeted kinase inhibition. 相似文献