全文获取类型
收费全文 | 1383篇 |
免费 | 92篇 |
专业分类
1475篇 |
出版年
2023年 | 11篇 |
2022年 | 11篇 |
2021年 | 37篇 |
2020年 | 26篇 |
2019年 | 38篇 |
2018年 | 43篇 |
2017年 | 27篇 |
2016年 | 47篇 |
2015年 | 65篇 |
2014年 | 79篇 |
2013年 | 85篇 |
2012年 | 84篇 |
2011年 | 90篇 |
2010年 | 56篇 |
2009年 | 62篇 |
2008年 | 70篇 |
2007年 | 67篇 |
2006年 | 87篇 |
2005年 | 65篇 |
2004年 | 63篇 |
2003年 | 61篇 |
2002年 | 33篇 |
2001年 | 22篇 |
2000年 | 15篇 |
1999年 | 24篇 |
1998年 | 13篇 |
1997年 | 10篇 |
1996年 | 19篇 |
1995年 | 8篇 |
1994年 | 9篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1981年 | 4篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1971年 | 4篇 |
1970年 | 3篇 |
1969年 | 6篇 |
1968年 | 2篇 |
排序方式: 共有1475条查询结果,搜索用时 15 毫秒
51.
Dalloul AH Patry C Salamero J Canque B Grassi F Schmitt C 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(10):5821-5828
Whether thymic dendritic cells (DC) are phenotypically and functionally distinct from the monocyte lineage DC is an important question. Human thymic progenitors differentiate into T, NK, and DC. The latter induce clonal deletion of autoreactive thymocytes and therefore might be different from their monocyte-derived counterparts. The cytokines needed for the differentiation of DC from thymic progenitors were also questioned, particularly the need for GM-CSF. We show that various cytokine combinations with or without GM-CSF generated DC from CD34+CD1a- but not from CD34+CD1a+ thymocytes. CD34+ thymic cells generated far fewer DC than their counterparts from the cord blood. The requirement for IL-7 was strict whereas GM-CSF was dispensable but nonetheless improved the yield of DC. CD14+ monocytic intermediates were not detected in these cultures unless macrophage-CSF (M-CSF) was added. Cultures in M-CSF generated CD14-CD1a+ DC precursors but also CD14+CD1a- cells. When sorted and recultured in GM-CSF, CD14+ cells down-regulated CD14 and up-regulated CD1a. TNF-alpha accelerated the differentiation of progenitors into DC and augmented MHC class II transport to the membrane, resulting in improved capacity to induce MLR. The trafficking of MHC class II molecules was studied by metabolic labeling and immunoprecipitation. MHC class II molecules were transported to the membrane in association with invariant chain isoforms in CD14+ (monocyte)-derived and in CD1a+ thymic-derived DC but not in monocytes. Thus, thymic progenitors can differentiate into DC along a preferential CD1a+ pathway but have conserved a CD14+ maturation capacity under M-CSF. Finally, CD1a+-derived thymic DC and monocyte-derived DC share very close Ag-processing machinery. 相似文献
52.
53.
54.
Claudia Alejandra Reyes-Valdez Gorgonio Ruiz-Campos Faustino Camarena-Rosales José Luis Castro-Aguirre Giacomo Bernardi 《Reviews in Fish Biology and Fisheries》2011,21(3):543-558
The population morphometric variation of the endangered freshwater killifish (Fundulus lima) was evaluated and compared with that of its euryhaline coastal relatives (F. parvipinnis parvipinnis and F. p. brevis) on the basis of 384 specimens from the Baja California peninsula, Mexico. Forty five standardized body distances were compared
by means of discriminant function analysis (DFA). Sixteen body distances were significant to distinguish two groups of populations
for F. lima: a first group represented by the Bebelamas and San Javier basins, and second group composed by the basins of San Ignacio,
La Purísima, San Luis, San Pedro and Las Pocitas. When all freshwater and coastal populations were compared, the southernmost
population of F. lima (Las Pocitas) showed a higher morphometric similarity with the southern coastal subspecies (F. p. brevis), while another southern population (San Pedro) had an intermediate position between the freshwater and coastal forms. This
study suggests the presence of five evolutionary units (three freshwater and two coastal) for the genus Fundulus in the Baja California peninsula. 相似文献
55.
Salani S Donadoni C Rizzo F Bresolin N Comi GP Corti S 《Journal of cellular and molecular medicine》2012,16(7):1353-1364
Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders characterized by progressive muscle wasting and weakness likely associated with exhaustion of muscle regeneration potential. At present, no cures or efficacious treatments are available for these diseases, but cell transplantation could be a potential therapeutic strategy. Transplantation of myoblasts using satellite cells or other myogenic cell populations has been attempted to promote muscle regeneration, based on the hypothesis that the donor cells repopulate the muscle and contribute to its regeneration. Embryonic stem cells (ESCs) and more recently induced pluripotent stem cells (iPSCs) could generate an unlimited source of differentiated cell types, including myogenic cells. Here we review the literature regarding the generation of myogenic cells considering the main techniques employed to date to elicit efficient differentiation of human and murine ESCs or iPSCs into skeletal muscle. We also critically analyse the possibility of using these cellular populations as an alternative source of myogenic cells for cell therapy of MDs. 相似文献
56.
Roberto Bovara Giacomo Carrea Sergio Riva Francesco Secundo 《Biotechnology letters》1996,18(3):305-308
Summary Cholic acid (3,7,12-trihydroxy-5-cholanoic acid) was completely and selectively transformed into 12-ketoursodeoxycholic acid (3,7-dihydroxy-12-oxo-5-cholanoic acid) by means of two consecutive enzymatic steps catalyzed, the first, by 7- and 12-hydroxysteroid dehydrogenase and, the second, by 7-hydroxysteroid dehydrogenase. Coenzyme regeneration was carried out with -ketoglutarate-glutamate dehydrogenase and glucose-glucose dehydrogenase, respectively. 相似文献
57.
Claudia Compagnucci Sara Di Siena Maria Blaire Bustamante Daniele Di Giacomo Monia Di Tommaso Mauro Maccarrone Paola Grimaldi Claudio Sette 《PloS one》2013,8(1)
Neural stem cells (NSCs) are self-renewing cells that can differentiate into multiple neural lineages and repopulate regions of the brain after injury. We have investigated the role of endocannabinoids (eCBs), endogenous cues that modulate neuronal functions including neurogenesis, and their receptors CB1 and CB2 in mouse NSCs. Real-time PCR and Western blot analyses indicated that CB1 is present at higher levels than CB2 in NSCs. The eCB anandamide (AEA) or the CB1-specific agonist ACEA enhanced NSC differentiation into neurons, but not astrocytes and oligodendrocytes, whereas the CB2-specific agonist JWH133 was ineffective. Conversely, the effect of AEA was inhibited by CB1, but not CB2, antagonist, corroborating the specificity of the response. CB1 activation also enhanced maturation of neurons, as indicated by morphometric analysis of neurites. CB1 stimulation caused long-term inhibition of the ERK1/2 pathway. Consistently, pharmacological inhibition of the ERK1/2 pathway recapitulated the effects exerted by CB1 activation on neuronal differentiation and maturation. Lastly, gene array profiling showed that CB1 activation augmented the expression of genes involved in neuronal differentiation while decreasing that of stemness genes. These results highlight the role of CB1 in the regulation of NSC fate and suggest that its activation may represent a pro-neuronal differentiation signal. 相似文献
58.
CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers 总被引:1,自引:0,他引:1
Filaci G Fenoglio D Fravega M Ansaldo G Borgonovo G Traverso P Villaggio B Ferrera A Kunkl A Rizzi M Ferrera F Balestra P Ghio M Contini P Setti M Olive D Azzarone B Carmignani G Ravetti JL Torre G Indiveri F 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(7):4323-4334
Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+ CD28- T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+ CD28- T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+ CD25+ T regulatory lymphocytes associate with CD8+ CD28- T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer. 相似文献
59.
Lasanthi-Kudahettige R Magneschi L Loreti E Gonzali S Licausi F Novi G Beretta O Vitulli F Alpi A Perata P 《Plant physiology》2007,144(1):218-231
60.
Vincent B Paitel E Saftig P Frobert Y Hartmann D De Strooper B Grassi J Lopez-Perez E Checler F 《The Journal of biological chemistry》2001,276(41):37743-37746
We showed previously that PrPc undergoes constitutive and phorbol ester-regulated cleavage inside the 106-126 toxic domain of the protein, leading to the production of a fragment referred to as N1. Here we show by a pharmacological approach that o-phenanthroline, a general zinc-metalloprotease inhibitors, as well as BB3103 and TAPI, the inhibitors of metalloenzymes ADAM10 (A disintegrin and metalloprotease); and TACE, tumor necrosis factor alpha-converting enzyme; ADAM17), respectively, drastically reduce N1 formation. We set up stable human embryonic kidney 293 transfectants overexpressing human ADAM10 and TACE, and we demonstrate that ADAM10 contributes to constitutive N1 production whereas TACE mainly participates in regulated N1 formation. Furthermore, constitutive N1 secretion is drastically reduced in fibroblasts deficient for ADAM10 whereas phorbol 12,13-dibutyrate-regulated N1 production is fully abolished in TACE-deficient cells. Altogether, our data demonstrate for the first time that disintegrins could participate in the catabolism of glycosyl phosphoinositide-anchored proteins such as PrPc. Second, our study identifies ADAM10 and ADAM17 as the protease candidates responsible for normal cleavage of PrPc. Therefore, these disintegrins could be seen as putative cellular targets of a therapeutic strategy aimed at increasing normal PrPc breakdown and thereby depleting cells of the putative 106-126 "toxic" domain of PrPc. 相似文献