全文获取类型
收费全文 | 1220篇 |
免费 | 64篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 28篇 |
2017年 | 18篇 |
2016年 | 25篇 |
2015年 | 38篇 |
2014年 | 60篇 |
2013年 | 82篇 |
2012年 | 94篇 |
2011年 | 91篇 |
2010年 | 53篇 |
2009年 | 47篇 |
2008年 | 82篇 |
2007年 | 71篇 |
2006年 | 57篇 |
2005年 | 63篇 |
2004年 | 50篇 |
2003年 | 55篇 |
2002年 | 53篇 |
2001年 | 12篇 |
2000年 | 19篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 10篇 |
1995年 | 12篇 |
1994年 | 12篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 16篇 |
1989年 | 20篇 |
1988年 | 6篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 9篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1968年 | 3篇 |
1965年 | 2篇 |
1963年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有1284条查询结果,搜索用时 15 毫秒
1.
2.
Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
3.
Carles Grau Romuald Ginhoux Alejandro Riera Thanh Lam Nguyen Hubert Chauvat Michel Berg Julià L. Amengual Alvaro Pascual-Leone Giulio Ruffini 《PloS one》2014,9(8)
Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. 相似文献
4.
Nicholas Cianciotto Terry Serwold-Davis Neal Groman Giulio Ratti Rino Rappuoli 《FEMS microbiology letters》1990,66(1-3):299-301
Chromosomal restriction fragments of Corynebacterium ulcerans and C. diphtheriae, containing an integration site for corynephages of the beta family, show homology on Southern blots. Homologous DNA in also found in the soil isolate C. glutamicum, although this strain is not susceptible to beta-corynephages. Three of these DNA fragments, one for each bacterial strain, and a fragment of gamma-corynephage DNA previously shown to contain the phage integration site, were cloned and sequenced. Alignment of the 3 bacterial sequences shows a very high degree of homology in a stretch of ca 120 nucleotides, whereas the rest of the sequences is generally non-homologous. Within this common bacterial portion, a segment of ca. 96 nucleotides (core sequence) is also highly homologous to the phage sequence. The first half (ca. 50 bp) of the core sequence is identical in all aligned sequences whereas the second half, which is largely occupied by a stem-and-loop structure, contains point mutations peculiar to each clone. The described sequences are likely to be involved in phage integration/excision processes. 相似文献
5.
The endogenous phosphorylation of human erythrocyte cytosolic proteins is markedly increased when the crude cytosol, prior to incubation in the presence of [y-32P] ATP, is submitted to DEAE-cellulose chromatography. Some proteins, including 22 and 23 kDa proteins, are preferentially phosphorylated by cytosolic casein kinase CS, whereas other proteins, including 42 kDa protein, are preferentially phosphorylated by casein kinase CTS. The CS-catalyzed phosphorylation is strongly inhibited by physiological ionic strength (150 mM KCl or NaCl) and by physiological levels (3 mM) of 2,3-bisphosphoglycerate, while CTS-catalyzed phosphorylation is unaffected. The very poor endogenous phosphorylation of these proteins in the crude cytosol may be due to the presence of other cytosolic inhibitors which are removed by DEAE-cellulose chromatography. 相似文献
6.
E Becchetti R Evangelisti M Bodo F Pezzetti A Orlacchio P Carinci 《Cellular and molecular biology, including cyto-enzymology》1989,35(2):187-198
During development the content of mesenchymal glycosaminoglycans (GAG) undergoes prominent changes, currently considered to act as regulatory signals in the epithelial-mesenchymal interactions. The factors involved in controlling GAG composition are as yet completely unknown. Lysosomal enzymes play a key role in GAG turnover. A possible mechanism for regulating GAG content could therefore be linked to developmental modulation of lysosomal glycosidases activity. We have examined the activity of the beta-N-acetyl-D-glucosaminidase (EC 3.2.1.30; a lysosomal hydrolase cleaving glycosidic linkage of the non-reducing terminal beta-N-acetyl-D-glucosamine residues) in chick embryo skin and lung (rudiments whose GAG composition has previously been studied) at various embryonic stages. Determinations were carried out on whole organs as well as on primary cultures of fibroblasts obtained from the two rudiments. beta-N-acetyl-D-glucosaminidase activity varied greatly during development, and it was significantly different in embryonic skin and lung tissues at various incubation days. In cultured fibroblasts, the enzymatic activity varied at different incubation days correlating with the in vivo data. Developmental changes of beta-N-acetyl-D-glucosaminidase paralleled mesenchymal GAG pattern both in vivo and in vitro. Our results, therefore, support the possibility that lysosomal enzymes could be involved in the regulation of mesenchymal GAG content during development. 相似文献
7.
Body wall organization in enchytraeids 总被引:2,自引:2,他引:0
Roberto Valvassori Magda de Eguileor Giulio Lanzavecchia Giorgio Scari 《Hydrobiologia》1989,180(1):83-89
The muscle organization of the body wall in some species of oligochaetes belonging to the Enchytraeus genus is described. No differences have been detected in their circular muscles, whereas longitudinal muscles show significant differences, allowing an easy identification of the various worm species. In particular, differences are noticeable in the external longitudinal layer. These observations suggest that structural and ultrastructural muscle fiber organizations can be used as a taxonomic tool. 相似文献
8.
Appearance of alpha-smooth muscle actin in human eye lens cells of anterior capsular cataract and in cultured bovine lens-forming cells 总被引:9,自引:0,他引:9
Annette Schmitt-Gräff Hans Pau Rolf Spahr Hans M. Piper Omar Skalli Giulio Gabbiani 《Differentiation; research in biological diversity》1990,43(2):115-122
Using light and electron-microscopic immunolocalization techniques, and gel electrophoresis combined with immunoblotting, we have examined the expression of cytoskeletal proteins in normal human fetal, child and adult lenses, in human anterior capsular cataract and in bovine lens cells in vivo and in vitro. In this report, we focus our observations on the pattern of actin-isoform expression during normal and pathological situations in vivo and culture conditions. We have noted that cells of developing and mature human lenses as well as bovine lens cells in situ contain only beta- and gamma-actins. In contrast, alpha-smooth muscle (alpha-sm) actin, an isoform typical of smooth muscle differentiation, was demonstrated in bovine lens cells at different times of culture. Moreover, the multilayered cells observed in the subcapsular zone of human anterior capsular cataract were characterized by the presence of alpha-sm actin. Thus, extensive changes in actin-isoform expression take place in lens cells growing in culture and may also occur during cataractogenesis. The biological meaning of the appearance of a marker of myoid differentiation in the ectodermally derived lens-forming cells is discussed. 相似文献
9.
Nerve growth factor and neuronal cell death 总被引:4,自引:0,他引:4
J. Regino Perez-Polo Perry J. Foreman George R. Jackson Din-e Shan Giulio Taglialatela Larry W. Thorpe Karin Werrbach-Perez 《Molecular neurobiology》1990,4(1-2):57-91
The regulation of neuronal cell death by the neuronotrophic factor, nerve growth factor (NGF), has been described during neural development and following injury to the nervous system. Also, reduced NGF activity has been reported for the aged NGF-responsive neurons of the sympathetic nervous system and cholinergic regions of the central nervous system (CNS) in aged rodents and man. Although there is some knowledge of the molecular structure of the NGF and its receptor, less is known as to the mechanism of action of NGF. Here, a possible role for NGF in the regulation of oxidant--antioxidant balance is discussed as part of a molecular explanation for the known effects of NGF on neuronal survival during development, after injury, and in the aged CNS. 相似文献
10.