全文获取类型
收费全文 | 1587篇 |
免费 | 64篇 |
专业分类
1651篇 |
出版年
2022年 | 5篇 |
2021年 | 13篇 |
2020年 | 7篇 |
2019年 | 4篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 26篇 |
2015年 | 42篇 |
2014年 | 53篇 |
2013年 | 69篇 |
2012年 | 122篇 |
2011年 | 86篇 |
2010年 | 70篇 |
2009年 | 66篇 |
2008年 | 95篇 |
2007年 | 106篇 |
2006年 | 86篇 |
2005年 | 110篇 |
2004年 | 101篇 |
2003年 | 112篇 |
2002年 | 90篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 16篇 |
1998年 | 41篇 |
1997年 | 13篇 |
1996年 | 21篇 |
1995年 | 16篇 |
1994年 | 21篇 |
1993年 | 20篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 15篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1971年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有1651条查询结果,搜索用时 0 毫秒
31.
Lefevre T Thomas F Schwartz A Levashina E Blandin S Brizard JP Le Bourligu L Demettre E Renaud F Biron DG 《Proteomics》2007,7(11):1908-1915
Despite increasing evidence of behavioural manipulation of their vectors by pathogens, the underlying mechanisms causing infected vectors to act in ways that benefit pathogen transmission remain enigmatic in most cases. Here, 2-D DIGE coupled with MS were employed to analyse and compare the head proteome of mosquitoes (Anopheles gambiae sensu stricto (Giles)) infected with the malarial parasite (Plasmodium berghei) with that of uninfected mosquitoes. This approach detected altered levels of 12 protein spots in the head of mosquitoes infected with sporozoites. These proteins were subsequently identified using MS and functionally classified as belonging to metabolic, synaptic, molecular chaperone, signalling, and cytoskeletal groups. Our results indicate an altered energy metabolism in the head of sporozoite-infected mosquitoes. Some of the up-/down-regulated proteins identified, such as synapse-associated protein, 14-3-3 protein and calmodulin, have previously been shown to play critical roles in the CNS of both invertebrates and vertebrates. Furthermore, a heat shock response (HSP 20) and a variation of cytoarchitecture (tropomyosins) have been shown. Discovery of these proteins sheds light on potential molecular mechanisms that underlie behavioural modifications and offers new insights into the study of intimate interactions between Plasmodium and its Anopheles vector. 相似文献
32.
33.
Anne Mouré Elodie Bacou Steffi Bosch Dominique Jegou Apolline Salama David Riochet Olivier Gauthier Gilles Blancho Jean-Paul Soulillou Denis Poncelet Eric Olmos Jean-Marie Bach Mathilde Mosser 《Biotechnology and bioengineering》2019,116(5):1176-1189
The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O2 supply after transplantation remains a major challenge. In this study, we address the O2 limitation by combining silicone-encapsulated CaO2 (silicone-CaO2) to generate O2 with an extracellular hemoglobin O2-carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O2-diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O2 species produced by silicone-CaO2. While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO2 alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO2 alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O2 provider with hemoglobin as an effective strategy to overcome O2 limitations in tissue engineering. 相似文献
34.
Christelle Monteil Caroline Leclere Franoise Dantzer Veronika Elkaz Jean-Paul Fillastre Jean-Paul Morin 《Cell biology international》1993,17(10):953-960
We have assessed the impact of increasing oxygen availability on cellular phenotype expression of rabbit proximal tubule cells in primary culture developed with variable glucose and/or insulin contents. To mitigate hypoxia at the cell/medium interface, cells were shaken for the whole culture duration and their expressed phenotype was compared with those expressed by static cultures. O2 and CO2 tensions were kept constant in the incubator atmosphere. Glycolysis and gluconeogenesis pathways, detoxication system, and mitochondrial, apical and basolateral membrane marker enzyme activities were assessed. This study showed that the induction of glycolysis which appear in primary cultures of proximal tubule cells may be partially prevented by continuously shaking the cultures. This effect was more marked in the presence of glucose, suggesting better substrate oxidation in shaken cultures. 相似文献
35.
Influence of age,castration, and testosterone on T cell subsets in healthy and leukemia grafted mice 总被引:1,自引:0,他引:1
Aboudkhil S Zaîd A Henry L Bureau JP 《Biology of the cell / under the auspices of the European Cell Biology Organization》2003,95(1):9-16
The distribution of T cell subsets in pubertal (2 months) and post-pubertal (10 months) mice showed a significant decrease in the percentage of CD4+ splenocytes and peripheral blood lymphocytes (PBL) with age, unlike the percentage of CD8+ cells in PBL, which remained unchanged. The change in the distribution of T cell subsets in the spleen and blood occurred in 2 months old castrated mice, as in 10 months old animals. P388 tumor grew better in post-pubertal and in castrated mice than in young mice. The intact mice survived longer than the castrated ones. The relative number of CD4+, CD8+ and CD2+ splenocytes was lower in transplanted intact mice than that in controls. The CD8+ and CD2+ subsets in the blood of 2 months transplanted mice were higher than those in controls, whereas in PBL, in 10 months old and castrated mice, the T lymphocyte subsets remain unchanged. Depo-testosterone (DT) injection strongly reduced weight and tumor growth in all the intact and castrated animals. A significant correlation is observed between the tumor weight and testosterone level in the plasma of the 2 months old DT treated mice. Moreover, DT injection induced a significant increase in the percentage of blood CD8+ cells in all the batches. These data indicate that physiologically, androgens affect the age-related distribution of lymphocyte T subsets and suggest that they slow down tumor growth, besides causing a direct effect, through an immunological process. 相似文献
36.
Cross-Reactions between the Cytotoxic T-Lymphocyte Responses of Human Immunodeficiency Virus-Infected African and European Patients 总被引:8,自引:5,他引:8 下载免费PDF全文
Deniz Durali Jacques Morvan Franck Letourneur Doris Schmitt Nelly Guegan Marc Dalod Sentob Saragosti Didier Sicard Jean-Paul Levy Elisabeth Gomard 《Journal of virology》1998,72(5):3547-3553
The great variability of protein sequences from human immunodeficiency virus (HIV) type 1 (HIV-1) isolates represents a major obstacle to the development of an effective vaccine against this virus. The surface protein (Env), which is the predominant target of neutralizing antibodies, is particularly variable. Here we examine the impact of variability among different HIV-1 subtypes (clades) on cytotoxic T-lymphocyte (CTL) activities, the other major component of the antiviral immune response. CTLs are produced not only against Env but also against other structural proteins, as well as some regulatory proteins. The genetic subtypes of HIV-1 were determined for Env and Gag from several patients infected either in France or in Africa. The cross-reactivities of the CTLs were tested with target cells expressing selected proteins from HIV-1 isolates of clade A or B or from HIV type 2 isolates. All African patients were infected with viruses belonging to clade A for Env and for Gag, except for one patient who was infected with a clade A Env-clade G Gag recombinant virus. All patients infected in France were infected with clade B viruses. The CTL responses obtained from all the African and all the French individuals tested showed frequent cross-reactions with proteins of the heterologous clade. Epitopes conserved between the viruses of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase, and the central region of Nef. Cross-reactivity also existed among Gag epitopes of clades A, B, and G, as shown by the results for the patient infected with the clade A Env-clade G Gag recombinant virus. These results show that CTLs raised against viral antigens from different clades are able to cross-react, emphasizing the possibility of obtaining cross-immunizations for this part of the immune response in vaccinated individuals. 相似文献
37.
Following the “Index of new names” (Theurillat & Moravec 1998), the present work collects the names of syntaxa (in the sense of the Code of phytosociological nomenclature,Barkman et al. 1986) above subassociation rank typified in 1994. The list comprises 101 names of syntaxa; three names are added to the Index 1992 (Theurillat & Moravec 1995). 相似文献
38.
Julien Deschênes Jean-Paul Valet Normand Marceau 《In vitro cellular & developmental biology. Plant》1980,16(8):722-729
Summary The two-step collagenase perfusion method originally developed for the high yield isolation of parenchymal cells from adult
rat livers has been adapted to rats of 1 day, 1 week, and 3 weeks of age. The use of this method to isolate hepatocytes from
five or six rats of the respective ages demonstrated its reliability in terms of cell yield, percentage of single cells, and
cell viability. In all cases, hepatocytes attach with high efficiency to fibronectin precoated dishes using serum-free culture
medium. The dynamics of spreading is faster for newborn hepatocytes than adult ones. The functional integrity of these parenchymal
liver cells was assessed by their capacity to secrete albumin and α-fetoprotein in serum-free medium and to express lactate
dehydrogenase activity over a 24-hr period in primary culture.
Part of this work was presented at the 30th Annual Meeting of the Tissue Culture Association, Seattle, June, 1979. 相似文献
39.
Reprogramming a nucleus by transferring it to oocyte cytoplasm triggers epigenetic changes that eventually lead to the restoration of a totipotent state and the birth of a viable animal. A simplified way of studying this complex process is to study cell hybrids. These studies suggest that the pluripotent character of one nucleus is dominant over that of the other nucleus. The development of nuclear transfer embryos shows that there are several restriction points and that the extra-embryonic lineages may be the primary source of death. Successful reprogramming depends on the balance between epigenetic modifications and the regulative properties of development. 相似文献
40.
Trafficking through Rab11 endosomes is required for cellularization during Drosophila embryogenesis 总被引:4,自引:0,他引:4
BACKGROUND: Embryonic cleavage leads to the formation of an epithelial layer during development. In Drosophila, the process is specialized and called cellularization. The trafficking pathways that underlie this process and that are responsible for the mobilization of membrane pools, however, remain poorly understood. RESULTS: We provide functional evidence for the role of endocytic trafficking through Rab11 endosomes in remobilizing vesicular membrane pools to ensure lateral membrane growth. Part of the membrane stems from endocytosed apical material. Mutants in the endocytic regulators rab5 and shibire/dynamin inhibit basal-lateral membrane growth, and apical endocytosis is blocked in shibire mutants. In addition, shibire controls vesicular trafficking through Rab11-positive endosomes. In shibire mutants, the transmembrane protein Neurotactin follows the secretory pathway normally but is not properly inserted in the plasma membrane and accumulates instead in Rab11 subapical endosomes. Consistent with a direct role of shibire in vesicular trafficking through Rab11 endosomes, Shibire is enriched in this compartment. Moreover, we show by electron microscopy the large accumulation of intracellular coated pits on subapical endocytic structures in shibire mutants. Finally, we show that Rab11 is essential for membrane growth and invagination during cellularization. CONCLUSION: Together, the data show that endocytic trafficking is required for basal-lateral membrane growth during cellularization. We identify Rab11 endosomes as key trafficking intermediates that control vesicle exocytosis and membrane growth during cellularization. This pathway may be required in other morphogenetic processes characterized by the growth of a membrane domain. 相似文献