全文获取类型
收费全文 | 581篇 |
免费 | 43篇 |
专业分类
624篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 16篇 |
2014年 | 17篇 |
2013年 | 28篇 |
2012年 | 22篇 |
2011年 | 33篇 |
2010年 | 17篇 |
2009年 | 14篇 |
2008年 | 25篇 |
2007年 | 23篇 |
2006年 | 26篇 |
2005年 | 29篇 |
2004年 | 17篇 |
2003年 | 13篇 |
2002年 | 21篇 |
2001年 | 27篇 |
2000年 | 18篇 |
1999年 | 15篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 16篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1985年 | 4篇 |
1981年 | 6篇 |
1979年 | 11篇 |
1977年 | 4篇 |
1976年 | 10篇 |
1975年 | 5篇 |
1974年 | 12篇 |
1973年 | 5篇 |
1972年 | 4篇 |
1966年 | 5篇 |
1965年 | 3篇 |
1964年 | 3篇 |
1962年 | 4篇 |
1961年 | 3篇 |
1922年 | 3篇 |
排序方式: 共有624条查询结果,搜索用时 15 毫秒
21.
Eddy van der Linden Bart W Faber Boris Bleijlevens Tanja Burgdorf Michael Bernhard B?rbel Friedrich Simon P J Albracht 《European journal of biochemistry》2004,271(4):801-808
The soluble, cytoplasmic NAD+-reducing [NiFe]-hydrogenase from Ralstonia eutropha is a heterotetrameric enzyme (HoxFUYH) and contains two FMN groups. The purified oxidized enzyme is inactive in the H2-NAD+ reaction, but can be activated by catalytic amounts of NADH. It was discovered that one of the FMN groups (FMN-a) is selectively released upon prolonged reduction of the enzyme with NADH. During this process, the enzyme maintained its tetrameric form, with one FMN group (FMN-b) firmly bound, but it lost its physiological activity--the reduction of NAD+ by H2. This activity could be reconstituted by the addition of excess FMN to the reduced enzyme. The rate of reduction of benzyl viologen by H2 was not dependent on the presence of FMN-a. Enzyme devoid of FMN-a could not be activated by NADH. As NADH-dehydrogenase activity was not dependent on the presence of FMN-a, and because FMN-b did not dissociate from the reduced enzyme, we conclude that FMN-b is functional in the NADH-dehydrogenase activity catalyzed by the HoxFU dimer. The possible function of FMN-a as a hydride acceptor in the hydrogenase reaction catalyzed by the HoxHY dimer is discussed. 相似文献
22.
J Trapman P Klaassen G G Kuiper J A van der Korput P W Faber H C van Rooij A Geurts van Kessel M M Voorhorst E Mulder A O Brinkmann 《Biochemical and biophysical research communications》1988,153(1):241-248
A cDNA clone has been isolated from a library prepared of mRNA of human breast cancer T47D cells with an oligonucleotide probe homologous to part of the region encoding the DNA-binding domain of steroid receptors. The clone has a size of 1505 bp and sequence analysis revealed an open reading frame of 1356 bp. The deduced amino acid sequence displays two highly conserved regions identified as the putative DNA-binding and hormone binding domains respectively of steroid receptors. Expression of this cDNA clone in COS cells produces a nuclear protein with all the binding characteristics of the human androgen receptor (hAR). The gene encoding the cDNA is assigned to the human X-chromosome. High levels of three hybridizing mRNA species of 11, 8.5 and 4.7 kb respectively are found in the human prostate cancer cell line (LNCaP), which contains elevated levels of hAR. The present data provide evidence that we have isolated a cDNA that encodes a major part of the human androgen receptor. 相似文献
23.
A. Hartog S. Hougee J. Faber A. Sanders C. Zuurman H.F. Smit P.M. van der Kraan M.A. Hoijer J. Garssen 《Phytomedicine》2008,15(5):313-320
Clinical studies have demonstrated that SKI306X, a purified preparation of three medicinal plants, relieves joint pain and improves functionality in osteoarthritis patients. To study the biological action of SKI306X, bovine cartilage explants and human peripheral blood mononuclear cells (PBMC) were stimulated with IL-1β and lipopolysaccharide (LPS) respectively, in the presence or absence of SKI306X and its individual composites. All tested compounds inhibited dose-dependently IL-1β-induced proteoglycan release and nitric oxide production by cartilage, indicating cartilage protective activity. SKI306X and two of its compounds inhibited PGE2, TNF- and IL-1β production by LPS-stimulated PBMC, indicating anti-inflammatory activity. These results demonstrate that the biological effect of SKI306X is at least bipartite: (1) cartilage protective and (2) anti-inflammatory. The observed anti-inflammatory effects may provide an explanation for the outcome of the clinical studies. Long-term clinical trails are necessary to elucidate whether the in vitro cartilage protective activity results in disease-modifying effects. 相似文献
24.
Jean-Marie Gasc Jack-Michel Renoir Lee E. Faber Francine Delahaye Etienne-Emile Baulieu 《Experimental cell research》1990,186(2):362-367
It has been proposed that the unliganded nontransformed form of steroid hormone receptor is a heterooligomer comprising, in addition to the hormone-binding subunit, two associated proteins: a heat shock protein of MW 90,000 (hsp90) and another protein of MW 59,000 (p59). Using monoclonal antibodies, we demonstrate immunocytochemically the presence of both hsp90 and p59 in cell nuclei of progesterone target cells of the rabbit uterus. While steroid receptors (e.g., progesterone receptors) appear to be exclusively nuclear, we find p59 predominantly in the cell nuclei and hsp90 in both the nucleus and the cytoplasm. In addition, Western blotting of high-salt extracts of nuclear proteins detects the presence of hsp90 and p59 in the nuclei of rabbit uterus. These observations are consistent with the presence of the untransformed heterooligomeric form of steroid hormone receptors in the nuclei of target cells. 相似文献
25.
Ortegel JW Staren ED Faber LP Warren WH Braun DP 《Cancer immunology, immunotherapy : CII》2000,48(11):627-634
The purpose of this work was to assess the capacity of tumor-infiltrating leukocytes (TIL) from human non-small-cell lung
carcinoma (NSCLC) specimens to synthesize type-1 and type-2 cytokines. Methods: TIL were isolated from tumors following digestion with collagenase/DNase and further enriched by ficoll-hypaque gradient
centrifugation. Membrane phenotypes and intracellular cytokine protein expression of TIL were assessed by flow cytometry.
Results: The majority of TIL expressed the CD3 antigen with a CD4:CD8 ratio of approximately 2:1. Other leukocytes such as macrophages
(CD14), B lymphocytes (CD20), and natural killer (NK) cells (CD56) were also found to infiltrate the tumors, but in significantly
lower numbers. Owing to the limited recovery of non-CD3+ leukocytes, our analysis of cytokine biosynthesis has focused on T lymphocytes. In the absence of activation, a small percentage
of CD3+ TIL synthesized cytokines ( <4%). Following activation with anti-CD3+interleukin-2 (IL-2), CD3+ TIL synthesized predominantly a type-1 cytokine profile; however, the type-2 cytokines, IL-6 and IL-10, were also detected
in a small percentage of infiltrating cells. Following activation with phorbol 12-myristate 13-acetate + ionomycin, CD3+ TIL also expressed more type-1 than type-2 cytokines and in significantly greater numbers of cells. The CD3+CD8+ component of the TIL synthesized only type-1 cytokines, whereas the CD3+CD4+ component synthesized both type-1 and type-2 cytokines. Conclusion: These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize
type-1 cytokines.
Received: 24 March 1999 / Accepted: 9 September 1999 相似文献
26.
N Massol M C Lebeau J M Renoir L E Faber E E Baulieu 《Biochemical and biophysical research communications》1992,187(3):1330-1335
FKBP59-HBI, a heat shock protein hsp90-binding immunophilin that was originally detected in heterooligomer forms of steroid receptors, is retained on Calmodulin (CAM)-Sepharose 4B in the presence of 2 mM Ca2+ and is eluted by EGTA, demonstrating a specific p59-CAM interaction. The p59 amino acid sequence reveals the presence of two putative CAM binding sites in a helix regions of the protein, as well as PEST sequences which are generally present in CAM-binding proteins. In vitro proteolysis by calpain II (a Ca(2+)-activated neutral protease), another feature of CAM-binding proteins, generates shorter peptides revealed by the mAb EC1, but not by the pAb 173 which recognizes the C-terminal of the protein. The potential function of CAM binding by the hsp90-binding immunophilin is discussed. 相似文献
27.
van Welsem T Frederiks F Verzijlbergen KF Faber AW Nelson ZW Egan DA Gottschling DE van Leeuwen F 《Molecular and cellular biology》2008,28(11):3861-3872
Dot1 methylates histone H3 lysine 79 (H3K79) on the nucleosome core and is involved in Sir protein-mediated silencing. Previous studies suggested that H3K79 methylation within euchromatin prevents nonspecific binding of the Sir proteins, which in turn facilitates binding of the Sir proteins in unmethylated silent chromatin. However, the mechanism by which the Sir protein binding is influenced by this modification is unclear. We performed genome-wide synthetic genetic array (SGA) analysis and identified interactions of DOT1 with SIR1 and POL32. The synthetic growth defects found by SGA analysis were attributed to the loss of mating type identity caused by a synthetic silencing defect. By using epistasis analysis, DOT1, SIR1, and POL32 could be placed in different pathways of silencing. Dot1 shared its silencing phenotypes with the NatA N-terminal acetyltransferase complex and the conserved N-terminal bromo adjacent homology (BAH) domain of Sir3 (a substrate of NatA). We classified all of these as affecting a common silencing process, and we show that mutations in this process lead to nonspecific binding of Sir3 to chromatin. Our results suggest that the BAH domain of Sir3 binds to histone H3K79 and that acetylation of the BAH domain is required for the binding specificity of Sir3 for nucleosomes unmethylated at H3K79. 相似文献
28.
29.
Irina A. Polejaeva Diane M. Broek Shawn C. Walker Wenli Zhou Mark Walton Abby D. Benninghoff David C. Faber 《PloS one》2013,8(12)
The objective of this study was to determine whether or not reproductive performance in cattle produced by somatic cell nuclear transfer (SCNT) is significantly different from that of their genetic donors. To address this question, we directed two longitudinal studies using different embryo production procedures: (1) superovulation followed by artificial insemination (AI) and embryo collection and (2) ultrasound-guided ovum pick-up followed by in vitro fertilization (OPU-IVF). Collectively, these two studies represent the largest data set available for any species on the reproductive performance of female clones and their genetic donors as measured by their embryo production outcomes in commercial embryo production program. The large-scale study described herein was conducted over a six-year period of time and provides a unique comparison of 96 clones to the 40 corresponding genetic donors. To our knowledge, this is the first longitudinal study on the reproductive performance of cattle clones using OPU-IVF. With nearly 2,000 reproductive procedures performed and more than 9,200 transferable embryos produced, our observations show that the reproductive performance of cattle produced by SCNT is not different compared to their genetic donors for the production of transferable embryos after either AI followed by embryo collection (P = 0.77) or OPU-IVF (P = 0.97). These data are in agreement with previous reports showing that the reproductive capabilities of cloned cattle are equal to that of conventionally produced cattle. In conclusion, results of this longitudinal study once again demonstrate that cloning technology, in combination with superovulation, AI and embryo collection or OPU-IVF, provides a valuable tool for faster dissemination of superior maternal genetics. 相似文献
30.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88