全文获取类型
收费全文 | 788篇 |
免费 | 80篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 8篇 |
2021年 | 23篇 |
2020年 | 15篇 |
2019年 | 20篇 |
2018年 | 18篇 |
2017年 | 18篇 |
2016年 | 27篇 |
2015年 | 41篇 |
2014年 | 46篇 |
2013年 | 52篇 |
2012年 | 66篇 |
2011年 | 53篇 |
2010年 | 36篇 |
2009年 | 31篇 |
2008年 | 42篇 |
2007年 | 45篇 |
2006年 | 38篇 |
2005年 | 36篇 |
2004年 | 30篇 |
2003年 | 35篇 |
2002年 | 24篇 |
2001年 | 13篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 18篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1974年 | 1篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 3篇 |
1968年 | 1篇 |
1965年 | 5篇 |
1963年 | 1篇 |
排序方式: 共有869条查询结果,搜索用时 15 毫秒
91.
The temporal stability of aggregate community properties depends on the dynamics of the component species. Since species growth can compensate for the decline of other species, synchronous species dynamics can maintain stability (i.e. invariability) in aggregate properties such as community abundance and metabolism. In field experiments we tested the separate and interactive effects of two stressors associated with storminess--loss of a canopy-forming species and mechanical disturbances--on species synchrony and community respiration of intertidal hard-bottom communities on Helgoland Island, NE Atlantic. Treatments consisted of regular removal of the canopy-forming seaweed Fucus serratus and a mechanical disturbance applied once at the onset of the experiment in March 2006. The level of synchrony in species abundances was assessed from estimates of species percentage cover every three months until September 2007. Experiments at two sites consistently showed that canopy loss significantly reduced species synchrony. Mechanical disturbance had neither separate nor interactive effects on species synchrony. Accordingly, in situ measurements of CO(2)-fluxes showed that canopy loss, but not mechanical disturbances, significantly reduced net primary productivity and temporal variation in community respiration during emersion periods. Our results support the idea that compensatory dynamics may stabilise aggregate properties. They further suggest that the ecological consequences of the loss of a single structurally important species may be stronger than those derived from smaller-scale mechanical disturbances in natural ecosystems. 相似文献
92.
93.
Candelaria M de la Cruz-Hernandez E Taja-Chayeb L Perez-Cardenas E Trejo-Becerril C Gonzalez-Fierro A Chavez-Blanco A Soto-Reyes E Dominguez G Trujillo JE Diaz-Chavez J Duenas-Gonzalez A 《PloS one》2012,7(3):e29181
Background
Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells.Methodology/Principal Findings
The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity.Conclusions/Significance
Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase. 相似文献94.
Catalina Trejo-Becerril Enrique Pérez-Cárdenas Lucía Taja-Chayeb Philippe Anker Roberto Herrera-Goepfert Luis A. Medina-Velázquez Alfredo Hidalgo-Miranda Delia Pérez-Montiel Alma Chávez-Blanco Judith Cruz-Velázquez José Díaz-Chávez Miguel Gaxiola Alfonso Due?as-González 《PloS one》2012,7(12)
It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy. 相似文献
95.
Leblond CS Heinrich J Delorme R Proepper C Betancur C Huguet G Konyukh M Chaste P Ey E Rastam M Anckarsäter H Nygren G Gillberg IC Melke J Toro R Regnault B Fauchereau F Mercati O Lemière N Skuse D Poot M Holt R Monaco AP Järvelä I Kantojärvi K Vanhala R Curran S Collier DA Bolton P Chiocchetti A Klauck SM Poustka F Freitag CM Waltes R Kopp M Duketis E Bacchelli E Minopoli F Ruta L Battaglia A Mazzone L Maestrini E Sequeira AF Oliveira B Vicente A Oliveira G Pinto D Scherer SW Zelenika D 《PLoS genetics》2012,8(2):e1002521
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. 相似文献
96.
97.
M. E. Oliva † I. M. Valdivia ¶ G. Costa ‡ N. Freitas ‡ M. A. Pinheiro De Carvalho‡ L. Sánchez § J. L. Luque 《Journal of fish biology》2008,72(3):545-554
The metazoan parasites of four populations of the chub mackerel Scomber japonicus were analysed from two localities in the Atlantic Ocean (Madeira Islands, Portugal, and Rio de Janeiro, Brazil) and two localities in the Pacific Ocean (Callao, Peru, and Antofagasta, Chile), collected during 2002 and 2003. A total of 373 fish specimens were studied and 34 metazoan parasite species were obtained. Parasites identified from the populations of chub mackerel studied could be separated into three categories: parasites with a wide distribution, present in the Pacific and Atlantic, parasites proper of the Pacific Ocean and parasites proper of the Atlantic Ocean. The analyses of some highly specific parasites of the genus Scomber ( i.e. monogeneans of the genus Kuhnia and didymozoid digeneans) strongly suggest the need for a revision of the taxonomic status of chub mackerels from the Atlantic and Pacific coast of America. The results demonstrated the usefulness of parasites as adequate tools to clarify the taxonomic status of their hosts. 相似文献
98.
Catalina Monzón-Argüello Joaquín Muñoz Adolfo Marco Luis Felipe López-Jurado Ciro Rico 《Conservation Genetics》2008,9(4):1045-1049
We describe 12 new polymorphic dinucleotide microsatellite loci and multiplex Polymerase Chain Reaction conditions from the
loggerhead sea turtle Caretta caretta. Levels of polymorphism were assessed in 50 individuals from the nesting population of the Cape Verde Islands. Number of
alleles ranged from 3 to 13 (average of 7.33) and the values of observed heterozygosities from 0.32 to 0.80 (average of 0.61).
Cross-species amplification on three other marine turtles, Chelonia mydas, Eretmochelys imbricata and Dermochelys coriacea, revealed polymorphism and variability at eight, eleven and three loci, respectively. 相似文献
99.
The obligate intracellular bacterial pathogen Chlamydia trachomatis replicates within a large vacuole or "inclusion" that expands as bacteria multiply but is maintained as an intact organelle. Here, we report that the inclusion is encased in a scaffold of host cytoskeletal structures made up of a network of F-actin and intermediate filaments (IF) that act cooperatively to stabilize the pathogen-containing vacuole. Formation of F-actin at the inclusion was dependent on RhoA, and its disruption led to the disassembly of IFs, loss of inclusion integrity, and leakage of inclusion contents into the host cytoplasm. In addition, IF proteins were processed by the secreted chlamydial protease CPAF to form filamentous structures at the inclusion surface with altered structural properties. We propose that Chlamydia has co-opted the function of F-actin and IFs to stabilize the inclusion with a dynamic, structural scaffold while minimizing the exposure of inclusion contents to cytoplasmic innate immune-surveillance pathways. 相似文献
100.