全文获取类型
收费全文 | 2747篇 |
免费 | 180篇 |
出版年
2023年 | 12篇 |
2022年 | 37篇 |
2021年 | 69篇 |
2020年 | 59篇 |
2019年 | 57篇 |
2018年 | 47篇 |
2017年 | 56篇 |
2016年 | 95篇 |
2015年 | 137篇 |
2014年 | 162篇 |
2013年 | 205篇 |
2012年 | 264篇 |
2011年 | 254篇 |
2010年 | 146篇 |
2009年 | 109篇 |
2008年 | 196篇 |
2007年 | 157篇 |
2006年 | 142篇 |
2005年 | 138篇 |
2004年 | 115篇 |
2003年 | 101篇 |
2002年 | 78篇 |
2001年 | 17篇 |
2000年 | 12篇 |
1999年 | 21篇 |
1998年 | 22篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1984年 | 5篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1978年 | 6篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1973年 | 6篇 |
1968年 | 11篇 |
1966年 | 4篇 |
1965年 | 3篇 |
1964年 | 5篇 |
1962年 | 5篇 |
1957年 | 5篇 |
1955年 | 3篇 |
排序方式: 共有2927条查询结果,搜索用时 718 毫秒
221.
222.
223.
Molecular cloning of IGF-1 and IGF-1 receptor and their expression pattern in the Chilean flounder (Paralichthys adspersus) 总被引:1,自引:0,他引:1
224.
Naves MA Pereira RM Comodo AN de Alvarenga EL Caparbo VF Teixeira VP 《Cell biology international》2011,35(11):1147-1151
Adhesive interactions play a critical role in cell biology, influencing vital processes from proliferation to cell death. Integrins regulate cell-ECM (extracellular matrix) adhesion and must associate with phosphorylating proteins such as ILK (integrin-linked kinase). Dysregulation of ILK expression is associated with anchorage-independent growth, cell survival and inhibition of apoptosis. Glucocorticoids influence differentiation and adhesion of osteoblasts and can affect bone protein synthesis. The objective of this study was to analyse the effect of DEX (dexamethasone) on the biology of osteoblasts, together with its influence on the expression of ILK and β1 integrin. For this, primary cultures of human osteoblasts were exposed to DEX at 10-9 M (physiological dose) and 10-6 M (pharmacological dose) for 24 and 48 h. Cell viability, apoptosis and cell adhesion were analysed, as well as protein expression of β1 integrin and ILK. It was observed that cell viability and adhesion were reduced in the cultures evaluated. In comparison with the control cultures, there was slightly less apoptosis in the cultures exposed to the physiological dose and considerably more apoptosis in those exposed to the pharmacological dose. In all treated cultures, protein expression of ILK was slightly higher than in the control cultures, whereas that of β1 integrin was significantly lower. Both proteins under study were co-localized at the cell periphery in all cultures. Our results suggest that DEX causes osteoblast anoikis, probably due to decreased β1 integrin expression, which might have had a direct influence upon ILK, reducing its activation and preventing it from playing its characteristic anti-apoptotic role. 相似文献
225.
Horn SR Thomenius MJ Johnson ES Freel CD Wu JQ Coloff JL Yang CS Tang W An J Ilkayeva OR Rathmell JC Newgard CB Kornbluth S 《Molecular biology of the cell》2011,22(8):1207-1216
Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/C(Cdh1) (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division. 相似文献
226.
Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. 相似文献
227.
228.
Tsuji T Matsuzaki J Ritter E Miliotto A Ritter G Odunsi K Old LJ Gnjatic S 《PloS one》2011,6(8):e23651
Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4(+) and CD8(+) T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8(+) T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4(+) T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4(+) T cells but not CD8(+) T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4(+) T cells in healthy donors originated from a CD45RA(-) antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4(+) T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events. 相似文献
229.
Kazuki Harada Erika Morimoto Yasushi Kataoka Toshio Takahashi 《Acta veterinaria Scandinavica》2011,53(1):11
Although the dog breeding industry is common in many countries, the presence of antimicrobial resistant bacteria among pups
in kennels has been infrequently investigated. This study was conducted to better understand the epidemiology of antimicrobial-resistant
Escherichia coli isolates from kennel pups not treated with antimicrobials. We investigated susceptibilities to 11 antimicrobials, and prevalence
of extended-spectrum β-lactamase (ESBL) in 86 faecal E. coli isolates from 43 pups in two kennels. Genetic relatedness among all isolates was assessed using pulsed-field gel electrophoresis
(PFGE). Susceptibility tests revealed that 76% of the isolates were resistant to one or more of tested antimicrobials, with
resistance to dihydrostreptomycin most frequently encountered (66.3%) followed by ampicillin (60.5%), trimethoprim-sulfamethoxazole
(41.9%), oxytetracycline (26.7%), and chloramphenicol (26.7%). Multidrug resistance, defined as resistance against two or
more classes of antimicrobials, was observed in 52 (60.5%) isolates. Three pups in one kennel harboured SHV-12 ESBL-producing
isolates. A comparison between the two kennels showed that frequencies of resistance against seven antimicrobials and the
variation in resistant phenotypes differed significantly. Analysis by PFGE revealed that clone sharing rates among pups of
the same litters were not significantly different in both kennels (64.0% vs. 88.9%), whereas the rates among pups from different litters were significantly different between the two kennels (72.0% vs. 33.3%, P < 0.05). The pups in the two kennels had antimicrobial-resistant E. coli clones, including multidrug-resistant and ESBL-producing clones. It is likely that resistant and susceptible bacteria can
clonally spread among the same and/or different litters thus affecting the resistance prevalence. 相似文献
230.
Manzoni C Colombo L Bigini P Diana V Cagnotto A Messa M Lupi M Bonetto V Pignataro M Airoldi C Sironi E Williams A Salmona M 《PloS one》2011,6(9):e24909
Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1-40 and Aβ 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity. 相似文献