全文获取类型
收费全文 | 326篇 |
免费 | 32篇 |
专业分类
358篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 17篇 |
2015年 | 13篇 |
2014年 | 18篇 |
2013年 | 21篇 |
2012年 | 32篇 |
2011年 | 27篇 |
2010年 | 15篇 |
2009年 | 18篇 |
2008年 | 24篇 |
2007年 | 19篇 |
2006年 | 18篇 |
2005年 | 12篇 |
2004年 | 20篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有358条查询结果,搜索用时 15 毫秒
41.
Nasser MW Datta J Nuovo G Kutay H Motiwala T Majumder S Wang B Suster S Jacob ST Ghoshal K 《The Journal of biological chemistry》2008,283(48):33394-33405
42.
M. G. Rosenblum Lawrence Cheung S. K. Kim Kalpana Mujoo Nicholas J. Donato James L. Murray 《Cancer immunology, immunotherapy : CII》1996,42(2):115-121
The development of cellular resistance to immunotoxins has been demonstrated in a variety of models and can involve a number
of mechanisms. For the present study, an immunotoxin was utilized composed of an antimelanoma antibody ZME-018 recognizing
a 240-kDa surface glycoprotein (gp 240) and the plant toxin gelonin. Human melanoma cells (A375-M) were grown in the presence
of increasing amounts of ZME-gelonin and a clonal variant (A-375-ZR) was developed that was 100-fold resistant to ZME-gelonin
compared to parental cells. Scatchard analysis showed that the A375-M parental cells had 260×103 ZME-gelonin-binding sites/cell with relatively low affinity (5 nM). In contrast, resistant A375-ZR cells demonstrated a reduced
number of low-affinity sites (160×103/cell), but showed a small number (47×103) of higher-affinity sites (0.8 nM). Internalization rates and degradation rates of 125I-labeled ZME-gelonin were identical in both the parental and resistant cells. A375-ZR cells were found to be more resistant
to vincristine and doxorubicin than were parental cells. Both cell lines were almost equally sensitive to native gelonin,
5-fluorouracil (5-FU), cisplatin, melphalan, carmustine, interferon γ (IFNγ) and IFNα. In addition, both cell lines were equally
sensitive to another gelonin-antibody conjugate that binds to cell-surface, GD2 (antibody 14G2A). However, resistant cells were twice as sensitive to the cytotoxic effects of etoposide than were parental cells. Finally,
a variety of agents were tested in combination with ZME-gelonin against A375-ZR cells in an attempt to identify agents to
augment immunotoxin cytotoxic effects against resistant cells. The agents 5-FU, cisplatin, IFNγ, IFNα, and etoposide were
the most effective in augmenting the cytotoxicity of ZME-gelonin against resistant cells. These studies suggest that development
of resistance to one immunotoxin does not cause development of cross-resistance to other gelonin immunotoxins. Further, specific
biological response modifiers and chemotherapeutic agents may be effective in augmenting the effectiveness of immunotoxins
and specifically targeting or reducing the emergence of immunotoxin-resistant cells.
Received: 15 March 1995 / Accepted: 28 November 1995 相似文献
43.
Aulophorus flabelliger Stephenson, 1931 is reported for the first time from Andrha Pradesh, India. 相似文献
44.
Biogas production has been shown to be inhibited by branched chain fatty acids (isobutyric, isovaleric) produced in the digester
by cellulolytic organisms. Performance of these mixed cellulolytic cultures isolated at 25°C (C25) and at 35° (C35) in a batch digester using cattle manure confirmed that C35, which forms mainly straight chain fatty acids from cellulose was more suitable for use as an inoculum than C25 which formed predominantly branched chain fatty acids. Reconstitution of cellulolytic culture C35 and mixed methanogens M35 almost doubled both the amount and rate of methane production. Cellulolytic culture was useful in pretreatment of water hyacinth
prior to its use as a substrate for methane generation A method for preservation and transportation of mixed cellulolytic
culture for use as an inoculum in the digester is described. 相似文献
45.
46.
Kalpana Singh Bhumika Chauhan Anshu Chaudhary Monica Misra Bindu Sharma Hridaya S Singh 《Bioinformation》2021,17(11):940
Thaparocleidus wallagonius is a monogenean parasite and a fish-borne pathogen with a worldwide distribution. The genome for Thaparocleidus wallagonius is known. Therefore, it is of interest to report the DNA motif analysis data in the 18S rDNA of Thaparocleidus wallagonius collected from the fish Wallago attu in India. This data forms a framework for an in-depth analysis of the parasite biology and development, immune evasion strategies, virulence and long-term survival within the definitive host. 相似文献
47.
Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema
Ahmad Y Shukla D Garg I Sharma NK Saxena S Malhotra VK Bhargava K 《Functional & integrative genomics》2011,11(3):407-417
We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem
time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20
patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found
that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components,
and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin β chain, transthyretin, and plasma retinol
binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis,
two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows
that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide
a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together,
our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE. 相似文献
48.
Pooja Dhupkar Huang Zhao Kalpana Mujoo Zhiqiang An Ningyan Zhang 《Biochemistry and Biophysics Reports》2016
Crk (C10 regulator of kinase) adaptor proteins are highly expressed in many types of human cancers and often contribute to aggressive cancer phenotypes. Crk II, a member of CRK family, has been reported to regulate cell migration and metastasis in breast cancer cells. However, its role in other cancer types has not been reported. In this study, we investigated the molecular function of Crk II in prostate cancer (PCa) cells (CWR-22rv1) in vitro and using a mouse tumor model. Results showed that Crk II knockdown by shRNA-mediated silencing (Crk II-shRNA) in the PCa cells significantly inhibited both cancer cell migration and invasion in cell culture study. Crk II-shRNA cancer cells also significantly decreased colony formation in vitro, but had no significant reduction of tumor volume after 4 weeks of cancer cell xenografting in vivo when compared to the scramble control. Interestingly, Crk II-shRNA cancer cells showed a greatly reduced level of insulin-like growth factor 1 receptor (IGF-1R) and decreased signaling of the IGF-1R/PI3K/Akt axis upon IGF-1 ligand stimulation. A close interaction between Crk II and IGF-1R was demonstrated upon co-immunoprecipitation of IGF-1R with Crk II protein. Further, treatment of cells with either proteosomal degradation or protein synthesis inhibitor showed higher proportion of ubiquitin-associated IGF-1R and faster degradation of IGF-1R in Crk II-shRNA cells in comparison with that in the control cancer cells. Taken together, these data suggest that Crk II plays an important role in the regulation of IGF-1R protein stability and affects downstream of IGF-1R signaling pathways. Therefore, targeting Crk-II can block IGF-1R growth signaling and suppress cancer cell invasion and progression. 相似文献
49.
Homodimerization of human bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) and its functional implications 总被引:1,自引:0,他引:1
Ghosh SS Sappal BS Kalpana GV Lee SW Chowdhury JR Chowdhury NR 《The Journal of biological chemistry》2001,276(45):42108-42115
Genetic lesions of bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) completely or partially abolish hepatic bilirubin glucuronidation, causing Crigler-Najjar syndrome type 1 or 2, respectively. Clinical observations indicate that some mutant forms of human UGT1A1 (hUGT1A1) may be dominant-negative, suggesting their interaction with the wild-type enzyme. To evaluate intermolecular interaction of hUGT1A1, Gunn rat fibroblasts were stably transduced with hUGT1A1 cDNA. Gel permeation chromatography of solubilized microsomes suggested dimerization of hUGT1A1 in solution. Nearest-neighbor cross-linking analysis indicated that, within microsomal membranes, hUGT1A1 dimerized more efficiently at pH 7.4 than at pH 9. Two-hybrid analysis in yeast and mammalian systems demonstrated positive interaction of hUGT1A1 with itself, but not with another UGT isoform, human UGT1A6, which differs only in the N-terminal domain. Dimerization was abolished by deletion of the membrane-embedded helix from the N-terminal domain of hUGT1A1, but not by substitution of several individual amino acid residues or partial deletion of the C-terminal domain. A C127Y substitution abolished UGT1A1 activity, but not its dimerization. Coexpression of mutagenized and wild-type hUGT1A1 in COS-7 cells showed that the mutant form markedly suppressed the catalytic activity of wild-type hUGT1A1. Homodimerization of hUGT1A1 may explain the dominant-negative effect of some mutant forms of the enzyme. 相似文献
50.
Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin 总被引:1,自引:0,他引:1
Bagaria A Surendranath K Ramagopal UA Ramakumar S Karande AA 《The Journal of biological chemistry》2006,281(45):34465-34474
Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate. 相似文献