全文获取类型
收费全文 | 2427篇 |
免费 | 176篇 |
国内免费 | 4篇 |
专业分类
2607篇 |
出版年
2023年 | 19篇 |
2022年 | 39篇 |
2021年 | 60篇 |
2020年 | 42篇 |
2019年 | 35篇 |
2018年 | 61篇 |
2017年 | 70篇 |
2016年 | 97篇 |
2015年 | 137篇 |
2014年 | 170篇 |
2013年 | 157篇 |
2012年 | 189篇 |
2011年 | 192篇 |
2010年 | 132篇 |
2009年 | 97篇 |
2008年 | 137篇 |
2007年 | 118篇 |
2006年 | 133篇 |
2005年 | 123篇 |
2004年 | 120篇 |
2003年 | 102篇 |
2002年 | 69篇 |
2001年 | 21篇 |
2000年 | 17篇 |
1999年 | 27篇 |
1998年 | 23篇 |
1997年 | 17篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 6篇 |
1992年 | 20篇 |
1991年 | 13篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 8篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
排序方式: 共有2607条查询结果,搜索用时 15 毫秒
71.
72.
In this study, we used a 16S rDNA–based approach to determine bacterial populations associated with coho salmon (Oncorhynchus kisutch) in its early life stages, highlighting dominant bacteria in the gastrointestinal tract during growth in freshwater. The present article is the first molecular analysis of bacterial communities of coho salmon. Cultivability of the salmon gastrointestinal microbiota was estimated by comparison of direct microscopic counts (using acridine orange) with colony counts (in tryptone soy agar). In general, a low fraction (about 1%) of the microbiota could be recovered as cultivable bacteria. Using DNA extracted directly from individuals belonging to the same lot, bacterial communities present in eggs and gastrointestinal tract of first-feeding fries and juveniles were monitored by polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE). The DGGE profiles revealed simple communities in all stages and exposed changes in bacterial community during growth. Sequencing and phylogenetic analysis of excised DGGE bands revealed the nature of the main bacteria found in each stage. In eggs, the dominant bacteria belonged to β-Proteobacteria (Janthinobacterium and Rhodoferax). During the first feeding stage, the most abundant bacteria in the gastrointestinal tract clustered with γ-Proteobacteria (Shewanella and Aeromonas). In juveniles ranging from 2 to 15 g, prevailing bacteria were Pseudomonas and Aeromonas. To determine the putative origin of dominant Pseudomonas and Aeromonas found in juvenile gastrointestinal tracts, primers for these groups were designed based on sequences retrieved from DGGE gel. Subsequently, samples of the water influent, pelletized feed, and eggs were analyzed by PCR amplification. Only those amplicons obtained from samples of eggs and the water influent presented identical sequences to the dominant bands of DGGE. Overall, our results suggest that a stable microbiota is established after the first feeding stages and its major components could be derived from water and egg epibiota. 相似文献
73.
Zhu B Guleria I Khosroshahi A Chitnis T Imitola J Azuma M Yagita H Sayegh MH Khoury SJ 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(6):3480-3489
Programmed death-1 (PD-1) is a negative costimulatory molecule, and blocking the interaction of PD-1 with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), enhances autoimmune disease in several animal models. We have studied the role of PD-1 ligands in disease susceptibility and chronic progression in experimental autoimmune encephalomyelitis (EAE). In BALB/c mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, PD-L1 but not PD-L2 blockade significantly increased EAE incidence. In B10.S mice immunized with myelin proteolipid protein (PLP) peptide 139-151, both PD-L1 and PD-L2 blockade markedly enhanced EAE severity. In prediabetic NOD mice immunized with PLP48-70, PD-L2 blockade worsened EAE but did not induce diabetes, whereas PD-L1 blockade precipitated diabetes but did not worsen EAE, suggesting different regulatory roles of these two ligands in EAE and diabetes. B6 mice immunized with MOG35-55 developed chronic persistent EAE, and PD-L2 blockade in the chronic phase exacerbated EAE, whereas PD-L1 blockade did not. In contrast, SJL/J mice immunized with PLP139-151 developed chronic relapsing-remitting EAE, and only PD-L1 blockade during remission precipitated EAE relapse. The strain-specific effects of PD-1 ligand blockade did not correlate with the expression of PD-L1 and PD-L2 on dendritic cells and macrophages in lymphoid tissue, or on inflammatory cells in the CNS. However, EAE enhancement is correlated with less prominent Th2 cytokine induction after specific PD-1 ligand blockade. In conclusion, PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain-specific manner. 相似文献
74.
75.
Small-world networks decrease the speed of Muller's ratchet 总被引:1,自引:0,他引:1
Muller's ratchet is an evolutionary process that has been implicated in the extinction of asexual species, the evolution of non-recombining genomes, such as the mitochondria, the degeneration of the Y chromosome, and the evolution of sex and recombination. Here we study the speed of Muller's ratchet in a spatially structured population which is subdivided into many small populations (demes) connected by migration, and distributed on a graph. We studied different types of networks: regular networks (similar to the stepping-stone model), small-world networks and completely random graphs. We show that at the onset of the small-world network - which is characterized by high local connectivity among the demes but low average path length - the speed of the ratchet starts to decrease dramatically. This result is independent of the number of demes considered, but is more pronounced the larger the network and the stronger the deleterious effect of mutations. Furthermore, although the ratchet slows down with increasing migration between demes, the observed decrease in speed is smaller in the stepping-stone model than in small-world networks. As migration rate increases, the structured populations approach, but never reach, the result in the corresponding panmictic population with the same number of individuals. Since small-world networks have been shown to describe well the real contact networks among people, we discuss our results in the light of the evolution of microbes and disease epidemics. 相似文献
76.
SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression 总被引:1,自引:0,他引:1 下载免费PDF全文
Jacobs KM Pennington JD Bisht KS Aykin-Burns N Kim HS Mishra M Sun L Nguyen P Ahn BH Leclerc J Deng CX Spitz DR Gius D 《International journal of biological sciences》2008,4(5):291-299
Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Two gene families have been shown to play a role in the genetic regulation of longevity; the Sirtuin and FOXO families. It is also established that nuclear Sirtuins interact with and under specific cellular conditions regulate the activity of FOXO gene family proteins. Thus, we hypothesize that a mitochondrial Sirtuin (SIRT3) might also interact with and regulate the activity of the FOXO proteins. To address this we used HCT116 cells overexpressing either wild-type or a catalytically inactive dominant negative SIRT3. For the first time we establish that FOXO3a is also a mitochondrial protein and forms a physical interaction with SIRT3 in mitochondria. Overexpression of a wild-type SIRT3 gene increase FOXO3a DNA-binding activity as well as FOXO3a dependent gene expression. Biochemical analysis of HCT116 cells over expressing the deacetylation mutant, as compared to wild-type SIRT3 gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that SIRT3 and FOXO3a comprise a potential mitochondrial signaling cascade response pathway. 相似文献
77.
The challenges encountered by proteomic researchers seeking diagnostic, prognostic and mechanistic markers were the subject of the 1-day meeting, Proteomics: Advances in Biomarker Discovery hosted by EuroSciCon. The speakers had a broad range of clinical and basic science interests, and presented data using a number of proteomic platforms to search for discriminant biomarkers of disease in easily accessible bodily fluids including serum and urine. Several potential pitfalls for proteomic researchers were mentioned and the potential of collaborative networks between research institutions to increase the size and power of clinical studies was discussed. Overall, the meeting highlighted the exciting opportunities that proteomic techniques offer for discovering not only diagnostic but also prognostic and mechanistic markers of a number of clinically important diseases. 相似文献
78.
Vieira NC Espíndola LS Santana JM Veras ML Pessoa OD Pinheiro SM de Araújo RM Lima MA Silveira ER 《Bioorganic & medicinal chemistry》2008,16(4):1676-1682
Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes. 相似文献
79.
The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein is responsible for the fusion between the membranes of the virus and the target cell. In the case of the S2 domain of protein S, it has been found a highly hydrophobic and interfacial domain flanked by the heptad repeat 1 and 2 regions; significantly, different peptides pertaining to this domain have shown a significant leakage effect and an important plaque formation inhibition, which, similarly to HIV-1 gp41, support the role of this region in the fusion process. Therefore, we have carried out a study of the binding and interaction with model membranes of a peptide corresponding to segment 1073–1095 of the SARS-CoV S glycoprotein, peptide SARSL in the presence of different membrane model systems, as well as the structural changes taking place in both the lipid and the peptide induced by the binding of the peptide to the membrane. Our results show that SARSL strongly partitions into phospholipid membranes and organizes differently in lipid environments, displaying membrane activity modulated by the lipid composition of the membrane. These data would support its role in SARS-CoV mediated membrane fusion and suggest that the region where this peptide resides could be involved in the merging of the viral and target cell membranes. 相似文献
80.
J. Jaime Miranda Victor M. Herrera Julio A. Chirinos Luis F. Gómez Pablo Perel Rafael Pichardo Angel González José R. Sánchez Catterina Ferreccio Ximena Aguilera Eglé Silva Myriam Oróstegui Josefina Medina-Lezama Cynthia M. Pérez Erick Suárez Ana P. Ortiz Luis Rosero Noberto Schapochnik Zulma Ortiz Daniel Ferrante Juan P. Casas Leonelo E. Bautista 《PloS one》2013,8(1)