全文获取类型
收费全文 | 1158篇 |
免费 | 70篇 |
出版年
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 20篇 |
2017年 | 8篇 |
2016年 | 40篇 |
2015年 | 49篇 |
2014年 | 44篇 |
2013年 | 71篇 |
2012年 | 67篇 |
2011年 | 80篇 |
2010年 | 48篇 |
2009年 | 40篇 |
2008年 | 66篇 |
2007年 | 49篇 |
2006年 | 58篇 |
2005年 | 36篇 |
2004年 | 53篇 |
2003年 | 51篇 |
2002年 | 33篇 |
2001年 | 26篇 |
2000年 | 32篇 |
1999年 | 22篇 |
1998年 | 15篇 |
1997年 | 14篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 13篇 |
1993年 | 14篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 21篇 |
1989年 | 12篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 21篇 |
1985年 | 19篇 |
1984年 | 4篇 |
1983年 | 10篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1969年 | 4篇 |
排序方式: 共有1228条查询结果,搜索用时 15 毫秒
91.
Ruiz-Herrera A García F Azzalin C Giulotto E Egozcue J Ponsà M Garcia M 《Human genetics》2002,110(6):578-586
The intrachromosomal location of the telomeric sequence in the crab-eating macaque, Macaca fascicularis (F. Cercopithecidae, Catarrhini) has been analysed by fluorescent in situ hybridisation with a long synthetic (TTAGGG)(n) probe. A total of 237 metaphases was analysed. As expected, all telomeres hybridised with the probe and 90 intrachromosomal loci with different hybridisation frequencies were also detected. The chromosomal location of interstitial telomeric sequences in M. fascicularis and in Homo sapiens was then compared, 37 sites (41.11%) being found to be conserved. Some of these sequences can be derived from rearrangements, such as inversions (MFA13q23) or fusions (MFA2p13 and MFA13p12), that have taken place during karyotype evolution. 相似文献
92.
Burlando B Evangelisti V Dondero F Pons G Camakaris J Viarengo A 《Biochemical and biophysical research communications》2002,291(3):476-483
Dictyostelium discoideum amoebae showed an uncommon resistance to Cu(2+), as pointed out through cell growth rate (EC(50) = 469 +/- 30 microM) and the neutral red cytotoxicity assay (EC(50) = 334 +/- 45 microM). Although no evidence of Cu-inducible metallothionein was found, Cu-dependent ATPase activity was cytochemically detected on pelletted, resin-embedded amoebae. This activity required Cu(2+) in the incubation medium, was sensitive to TPEN, vanadate and temperature, and showed dose-dependent increase after exposure of amoebae to 10-500 microM Cu(2+) for 7 days. Accordingly, immunofluorescence and Western blotting revealed the occurrence of a Cu-inducible, putative homologue of human Menkes (MNK) Cu-P-type ATPase. To verify if Cu-ATPase is involved in copper resistance, amoebae were exposed to low concentrations of Cu(2+) and vanadate followed by the neutral red assay. Exposure to either treatment showed no effect, while a combination caused a dramatic increase of Cu toxicity, possibly depending on Cu-ATPase inhibition. 相似文献
93.
Pere Pons Pierre-Yves Henry Gabriel Gargallo Roger Prodon Jean-Dominique Lebreton 《Population Ecology》2003,45(3):187-196
Post-disturbance survival is a key factor in the onset of secondary successions. Here we analyse capture-recapture data from two before/after disturbance studies to estimate the effect of fire on local bird survival. Analyses of six bird species at two Mediterranean shrubland sites were combined using a meta-analysis approach. Two warblers, Sylvia undata and S. melanocephala, were studied at one site altered by prescribed burning, and five passerines (Luscinia megarhynchos, Turdus merula, Parus major, P. caeruleus and S. melanocephala) at one site disturbed by wildfire. Based on the combined analysis, annual survival probability significantly decreased from 0.49 to 0.18 (i.e. a 64% decline) after the fire. Our results further suggest a trend for a higher decrease in annual survival associated with wildfire (–72%, from 0.51 to 0.14) than with prescribed burning (–35%, from 0.41 to 0.27), although this should be properly tested with a specific experimental design. In S. undata, a decline in survival in the long-term cannot account for the drop in density observed the first spring after fire. We suggest that a decrease in recruitment rate and an increase in the proportion of non-breeders immediately after the fire may contribute more strongly to the decline in the breeding population. Our results tend to support the idea that bird populations may respond to moderate disturbances with noticeable time lags, because of individual site tenacity. 相似文献
94.
95.
Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive 总被引:8,自引:0,他引:8
Winer S Tsui H Lau A Song A Li X Cheung RK Sampson A Afifiyan F Elford A Jackowski G Becker DJ Santamaria P Ohashi P Dosch HM 《Nature medicine》2003,9(2):198-205
Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100beta. pSC-autoreactive T- and B-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (NOD) mice, followed by progressive pSC destruction before detectable beta-cell death. Humans with probable prediabetes generate similar autoreactivities, and autoantibodies in islet-cell autoantibody (lCA) -positive sera co-localize to pSC. Moreover, GFAP-specific NOD T-cell lines transferred pathogenic peri-insulitis to NOD/severe combined immunodeficient (NOD/SCID) mice, and immunotherapy with GFAP or S100beta prevented diabetes. pSC survived in rat insulin promoter Iymphocytic choriomeningitis virus (rip-LCMV) glycoprotein/CD8+ T-cell receptor(gp) double-transgenic mice with virus-induced diabetes, suggesting that pSC death is not an obligate consequence of local inflammation and beta-cell destruction. However, pSC were deleted in spontaneously diabetic NOD mice carrying the CD8+/8.3 T-cell receptor transgene, a T cell receptor commonly expressed in earliest islet infiltrates. Autoimmune targeting of pancreatic nervous system tissue elements seems to be an integral, early part of natural type 1 diabetes. 相似文献
96.
Plant genome archaeology: evidence for conserved ancestral chromosome segments in dicotyledonous plant species 总被引:3,自引:0,他引:3
Dominguez I Graziano E Gebhardt C Barakat A Berry S Arús P Delseny M Barnes S 《Plant biotechnology journal》2003,1(2):91-99
We have developed genetic maps, based on expressed sequence tags (ESTs) that are homologous to Arabidopsis genes, in four dicotyledonous crop plant species from different families. A comparison of these maps with the physical map of Arabidopsis reveals common genome segments that appear to have been conserved throughout the evolution of the dicots. In the four crop species analysed these segments comprise between 16 and 33% of the Arabidopsis genome. Our findings extend the synteny patterns previously observed only within plant families, and indicate that structural and functional information from the model species will be, at least in part, applicable in crop plants with large genomes. 相似文献
97.
Destoumieux-Garzón D Thomas X Santamaria M Goulard C Barthélémy M Boscher B Bessin Y Molle G Pons AM Letellier L Peduzzi J Rebuffat S 《Molecular microbiology》2003,49(4):1031-1041
The mechanism of action of microcin E492 (MccE492) was investigated for the first time in live bacteria. MccE492 was expressed and purified to homogeneity through an optimized large-scale procedure. Highly purified MccE492 showed potent antibacterial activity at minimal inhibitory concentrations in the range of 0.02-1.2 microM. The microcin bactericidal spectrum of activity was found to be restricted to Enterobacteriaceae and specifically directed against Escherichia and Salmonella species. Isogenic bacteria that possessed mutations in membrane proteins, particularly of the TonB-ExbB-ExbD complex, were assayed. The microcin bactericidal activity was shown to be TonB- and energy-dependent, supporting the hypothesis that the mechanism of action is receptor mediated. In addition, MccE492 depolarized and permeabilized the E. coli cytoplasmic membrane. The membrane depolarization was TonB dependent. From this study, we propose that MccE492 is recognized by iron-siderophore receptors, including FepA, which promote its import across the outer membrane via a TonB- and energy-dependent pathway. MccE492 then inserts into the inner membrane, whereupon the potential becomes destabilized by pore formation. Because cytoplasmic membrane permeabilization of MccE492 occurs beneath the threshold of the bactericidal concentration and does not result in cell lysis, the cytoplasmic membrane is not hypothesized to be the sole target of MccE492. 相似文献
98.
Association of insulin receptor substrate 1 (IRS-1) y895 with Grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Valverde AM Mur C Pons S Alvarez AM White MF Kahn CR Benito M 《Molecular and cellular biology》2001,21(7):2269-2280
We have recently generated immortalized fetal brown adipocyte cell lines from insulin receptor substrate 1 (IRS-1) knockout mice and demonstrated an impairment in insulin-induced lipid synthesis as compared to wild-type cell lines. In this study, we investigated the consequences of IRS-1 deficiency on mitogenesis in response to insulin. The lack of IRS-1 resulted in the inability of insulin-stimulated IRS-1-deficient brown adipocytes to increase DNA synthesis and enter into S/G2/M phases of the cell cycle. These cells showed a severe impairment in activating mitogen-activated protein kinase kinase (MEK1/2) and p42-p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. IRS-1-deficient cells also lacked tyrosine phosphorylation of SHC and showed no SHC-Grb-2 association in response to insulin. The mitogenic response to insulin could be partially restored by enhancing IRS-2 tyrosine phosphorylation and its association with Grb-2 by inhibition of phosphatidylinositol 3-kinase activity through a feedback mechanism. Reconstitution of IRS-1-deficient brown adipocytes with wild-type IRS-1 restored insulin-induced IRS-1 and SHC tyrosine phosphorylation and IRS-1-Grb-2, IRS-1-SHC, and SHC-Grb-2 associations, leading to the activation of MAPK and enhancement of DNA synthesis. Reconstitution of IRS-1-deficient brown adipocytes with the IRS-1 mutant Tyr895Phe, which lacks IRS-1-Grb-2 binding, restored SHC-IRS-1 association and SHC-Grb-2 association. However, the lack of IRS-1-Grb-2 association impaired MAPK activation and DNA synthesis in insulin-stimulated mutant cells. These data provide strong evidence for an essential role of IRS-1 and its direct association with Grb-2 in the insulin signaling pathway leading to MAPK activation and mitogenesis in brown adipocytes. 相似文献
99.
Negrette B Bonilla E Valero N Pons H Garcia Tamayo J Chacín-Bonilla L Medina-Leendertz S Añez F 《Neurochemical research》2001,26(7):767-770
To determine whether treatment with melatonin (MLT) improves the efficiency of immunization against Venezuelan equine encephalomyelitis (VEE) virus, mice were vaccinated with TC-83 VEE virus and treated daily with MLT (1 or 5 mg/kg) starting 3 days before immunization, until 10 days after. IgM antibody titers were determined at days 7, 14, and 21 post-immunization. IL-10 levels were assayed at day 14 postvaccination. Treatment with MLT increased antibody titers 14 days after the immunization. IL-10 levels also increased with MLT treatment (1 and 5 mg/kg). Mice were challenged with live VEE virus at day 21 postimmunization, and viral titers were plaque assayed in chicken embryo fibroblasts 4 days after the infection. Following this challenge brain virus levels were significantly reduced. The results suggest that MLT treatment enhances the efficiency of mice immunization against VEE virus. 相似文献
100.
Pere Casals Joan Romanyà Jordi Cortina Pierre Bottner Marie-Madeleine Coûteaux V. Ramon Vallejo 《Biogeochemistry》2000,48(3):261-281
We studied the seasonality of total soil CO2efflux and labeled C-CO2 released from 14Clabeled straw incubated in the H horizon of asemi-arid Mediterranean forest soil. Fieldmeasurements were carried out over 520 days in aseries of reconstructed soil profiles with and withouta gravel layer below the H horizon. We monitored soilclimate and related this to soil CO2 efflux.Seasonal variations in soil CO2 efflux in asemiarid Mediterranean forest were mainly related tochanges in soil temperature. In spite of drought, highrespiration rates were observed in mid summer. Highsoil CO2 efflux in hot and dry episodes wasattributed to increases in soil biological activity.The minimum soil CO2 efflux occurred in latesummer also under dry conditions, probably related toa decrease in soil biological activity in deephorizons. Biological activity in organic layers waslimited by water potential () in summer and bytemperature in winter. Rewetting a dry soil resultedin large increases in soil CO2 efflux only at hightemperatures. These large increases represented asignificant contribution to the decomposition oforganic matter in the uppermost horizons. Soilbiological activity in the uppermost horizons was moresensitive to changes in soil and hence tosummer rainstorms than the bulk soil microbialactivity. The presence of a layer of gravel improvedboth moisture and temperature conditions for thedecomposition of organic matter. As a result, soilCO2 efflux increased in soils containing rockfragments. These effects were especially large for theorganic layers. 相似文献