全文获取类型
收费全文 | 639篇 |
免费 | 43篇 |
专业分类
682篇 |
出版年
2023年 | 8篇 |
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 9篇 |
2019年 | 24篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 21篇 |
2015年 | 29篇 |
2014年 | 21篇 |
2013年 | 30篇 |
2012年 | 48篇 |
2011年 | 34篇 |
2010年 | 21篇 |
2009年 | 23篇 |
2008年 | 25篇 |
2007年 | 30篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 21篇 |
2003年 | 23篇 |
2002年 | 23篇 |
2001年 | 8篇 |
2000年 | 16篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 15篇 |
1991年 | 6篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1980年 | 7篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1974年 | 6篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1966年 | 3篇 |
1960年 | 2篇 |
排序方式: 共有682条查询结果,搜索用时 0 毫秒
21.
We have broadly defined the DNA regions regulating esterase6 activity in
several life stages and tissue types of D. melanogaster using P-
element-mediated transformation of constructs that contain the esterase6
coding region and deletions or substitutions in 5' or 3' flanking DNA.
Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and
the primary sequences regulating its activity lie between -171 and -25 bp
relative to the translation initiation site: deletion of these sequences
decrease activity approximately 20-fold. Hemolymph activity is also
modulated by four other DNA regions, three of which lie 5' and one of which
lies 3' of the coding region. Of these, two have positive and two have
negative effects, each of approximately twofold. Esterase6 activity is
present also in two male reproductive tract tissues; the ejaculatory bulb,
which is another ancestral activity site, and the ejaculatory duct, which
is a recently acquired site within the melanogaster species subgroup.
Activities in these tissues are at least in part independently regulated:
activity in the ejaculatory bulb is conferred by sequences between -273 and
-172 bp (threefold decrease when deleted), while activity in the
ejaculatory duct is conferred by more distal sequences between -844 and
-614 bp (fourfold decrease when deleted). The reproductive tract activity
is further modulated by two additional DNA regions, one in 5' DNA (-613 to
-284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to
+2731 bp; threefold decrease when deleted) that probably overlaps the
adjacent esteraseP gene. Collating these data with previous studies
suggests that expression of EST6 in the ancestral sites is mainly regulated
by conserved proximal sequences while more variable distal sequences
regulate expression in the acquired ejaculatory duct site.
相似文献
22.
Eulália Silva dos Santos Pinheiro Fernanda Costa de Queirós Pedro Montoya Cleber Luz Santos Marion Alves do Nascimento Clara Hikari Ito Manuela Silva David Barros Nunes Santos Silvia Benevides José Garcia Vivas Miranda Katia Nunes Sá Abrah?o Fontes Baptista 《PloS one》2016,11(2)
The main objective of this study is to review and summarize recent findings on electroencephalographic patterns in individuals with chronic pain. We also discuss recent advances in the use of quantitative Electroencephalography (qEEG) for the assessment of pathophysiology and biopsychosocial factors involved in its maintenance over time. Data collection took place from February 2014 to July 2015 in PubMed, SciELO and PEDro databases. Data from cross-sectional studies and longitudinal studies, as well as clinical trials involving chronic pain participants were incorporated into the final analysis. Our primary findings related to chronic pain were an increase of theta and alpha EEG power at rest, and a decrease in the amplitude of evoked potentials after sensory stimulation and cognitive tasks. This review suggests that qEEG could be considered as a simple and objective tool for the study of brain mechanisms involved in chronic pain, as well as for identifying the specific characteristics of chronic pain condition. In addition, results show that qEEG probably is a relevant outcome measure for assessing changes in therapeutic studies. 相似文献
23.
Ricardo Sánchez David Pantoja-Uceda Jesús Prieto Tammo Diercks María J. Marcaida Guillermo Montoya Ramón Campos-Olivas Francisco J. Blanco 《The Journal of biological chemistry》2010,285(29):22196-22201
Gadd45α is a nuclear protein encoded by a DNA damage-inducible gene. Through its interactions with other proteins, Gadd45α participates in the regulation of DNA repair, cell cycle, cell proliferation, and apoptosis. The NMR structure of human Gadd45α has been determined and shows an α/β fold with two long disordered and flexible regions at the N terminus and one of the loops. Human Gadd45α is predominantly monomeric in solution but exists in equilibrium with dimers and other oligomers whose population increases with protein concentration. NMR analysis shows that Aurora A interacts through its N-terminal domain with a region of human Gadd45α encompassing the site of dimerization, suggesting that the oligomerization of Gadd45α could be a regulatory mechanism to modulate its interactions with Aurora A, and possibly with other proteins too. However, Gadd45α appears to interact only weakly with PCNA through its flexible loop, in contrast with previous and contradictory reports. 相似文献
24.
Black AP Bhayani H Ryder CA Pugh MT Gardner-Medwin JM Southwood TR 《Arthritis research & therapy》2003,5(5):R277-R284
The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients
with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to
a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients
with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients:
a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested;
and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial
fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients
without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association
between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence
recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses
to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells
in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association
between the acute phase response and the T cell population recruited to an inflammatory site. 相似文献
25.
F. González M. Esther Fárez-Vidal J.M. Arias E. Montoya 《Journal of applied microbiology》1994,77(5):567-573
F. GONZÁLEZ, M.E. FÁREZ-VIDAL, J.M. ARIAS AND E. MONTOYA. 1994. Acid phosphatase and alkaline phosphatase from vegetative cells of Myxococcus coralloides D were purified by two chromatographic steps. The molecular weights were estimated by gel filtration and SDS-PAGE. Optimum pH, stability, optimum temperature and thermal inactivation studies were made for both enzymes. EDTA and other chelating agents inhibited alkaline but not acid activity. Mg2+ activated the alkaline phosphatase, while the acid phosphatase was inhibited by fluoride. Both enzymes degraded a number of phosphomonoesters, but were unable to hydrolyse either polyphosphates or cAMP. The K m values of the acid and alkaline phosphatases for p -nitrophenylphosphate were 5.0 times 10-3 mol ***l-1 and 1.5 times 10-3 mol l-1 , respectively. 相似文献
26.
Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.27.
J.A. Poveda A.M. GiudiciM.L. Renart M.L. MolinaE. Montoya A. Fernández-CarvajalG. Fernández-Ballester J.A. EncinarJ.M. González-Ros 《生物化学与生物物理学报:生物膜》2014
Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids. The fact that this protein is able to assemble into clusters through the same non-annular sites, resulting in large changes in channel activity, makes these sites even more interesting as a potential target to develop lead compounds able to disrupt such interactions and hopefully, to modulate ion channel function. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. 相似文献
28.
Cats are important in the epidemiology of Toxoplasma gondii because felids are the only definitive hosts that can excrete environmentally resistant oocysts. Fresh samples of brain from 103 Spanish cats with antibodies to T. gondii were analyzed for T. gondii DNA using nested-PCR; 47 (45.5%) were found to be positive. Further characterization of DNA from 46 cats using RFLP-PCR at the 3' and 5' ends of the SAG2 locus revealed that 12 (26%) isolates were Type I and 34 (74%) were Type II; no Type III were found, and the 47th sample could not be classified to its genetic type. In addition, T. gondii was also isolated by bioassay in mice from 42 of 103 seropositive cats. This is the first report of T. gondii characterization from cats in Spain. 相似文献
29.
Carolina R. Melo-Silva Pedro Alves-Peixoto Natasha Heath Lingjuan Tang Brian Montoya Cory J. Knudson Colby Stotesbury Maria Ferez Eric Wong Luis J. Sigal 《PLoS pathogens》2021,17(5)
Type I interferons (IFN-I) are antiviral cytokines that signal through the ubiquitous IFN-I receptor (IFNAR). Following footpad infection with ectromelia virus (ECTV), a mouse-specific pathogen, C57BL/6 (B6) mice survive without disease, while B6 mice broadly deficient in IFNAR succumb rapidly. We now show that for survival to ECTV, only hematopoietic cells require IFNAR expression. Survival to ECTV specifically requires IFNAR in both natural killer (NK) cells and monocytes. However, intrinsic IFNAR signaling is not essential for adaptive immune cell responses or to directly protect non-hematopoietic cells such as hepatocytes, which are principal ECTV targets. Mechanistically, IFNAR-deficient NK cells have reduced cytolytic function, while lack of IFNAR in monocytes dampens IFN-I production and hastens virus dissemination. Thus, during a pathogenic viral infection, IFN-I coordinates innate immunity by stimulating monocytes in a positive feedback loop and by inducing NK cell cytolytic function. 相似文献
30.