全文获取类型
收费全文 | 421篇 |
免费 | 37篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 21篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 14篇 |
2015年 | 20篇 |
2014年 | 30篇 |
2013年 | 33篇 |
2012年 | 40篇 |
2011年 | 42篇 |
2010年 | 23篇 |
2009年 | 15篇 |
2008年 | 29篇 |
2007年 | 21篇 |
2006年 | 25篇 |
2005年 | 22篇 |
2004年 | 13篇 |
2003年 | 23篇 |
2002年 | 14篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有458条查询结果,搜索用时 31 毫秒
31.
32.
An important challenge in ecology is to predict patterns of biodiversity across eco‐geographical gradients. This is particularly relevant in areas that are inaccessible, but are of high research and conservation value, such as mountains. Potentially, remotely‐sensed vegetation indices derived from satellite images can help in predicting species diversity in vast and remote areas via their relationship with two of the major factors that are known to affect biodiversity: productivity and spatial heterogeneity in productivity. Here, we examined whether the Normalized Difference Vegetation Index (NDVI) can be used effectively to predict changes in butterfly richness, range size rarity and beta diversity along an elevation gradient. We examined the relationship between butterfly diversity and both the mean NDVI within elevation belts (a surrogate of productivity) and the variability in NDVI within and among elevation belts (surrogates for spatial heterogeneity in productivity). We calculated NDVI at three spatial extents, using a high spatial resolution QuickBird satellite image. We obtained data on butterfly richness, rarity and beta diversity by field sampling 100 m quadrats and transects between 500 and 2200 m in Mt Hermon, Israel. We found that the variability in NDVI, as measured both within and among adjacent elevation belts, was strongly and significantly correlated with butterfly richness. Butterfly range size rarity was strongly correlated with the mean and the standard deviation of NDVI within belts. In our system it appears that it is spatial heterogeneity in productivity rather than productivity per se that explained butterfly richness. These results suggest that remotely‐sensed data can provide a useful tool for assessing spatial patterns of butterfly richness in inaccessible areas. The results further indicate the importance of considering spatial heterogeneity in productivity along elevation gradients, which has no lesser importance than productivity in shaping richness and rarity, especially at the local scale. 相似文献
33.
The field of pharmacogenomics aims to predict which drugs will be most effective and safe for a particular individual based on their genome sequence or expression profile, thereby allowing personalized treatment. The bulk of pharmacogenomic research has focused on the role of single nucleotide polymorphisms, copy number variations or differences in gene expression levels of drug metabolizing or transporting genes and drug targets. In this review paper, we focus instead on microRNAs (miRNAs): small noncoding RNAs, prevalent in metazoans, that negatively regulate gene expression in many cellular processes. We discuss how miRNAs, by regulating the expression of pharmacogenomic-related genes, can play a pivotal role in drug efficacy and toxicity and have potential clinical implications for personalized medicine. 相似文献
34.
35.
PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells
Hendel A Krijger PH Diamant N Goren Z Langerak P Kim J Reissner T Lee KY Geacintov NE Carell T Myung K Tateishi S D'Andrea A Jacobs H Livneh Z 《PLoS genetics》2011,7(9):e1002262
Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity. 相似文献
36.
MOTIVATION: Early and accurate detection of human pathogen infection is critical for treatment and therapeutics. Here we describe pathogen identification using short RNA subtraction and assembly (SRSA), a detection method that overcomes the requirement of prior knowledge and culturing of pathogens, by using degraded small RNA and deep sequencing technology. We prove our approach's efficiency through identification of a combined viral and bacterial infection in human cells. 相似文献
37.
38.
Goldstein-Daruech N Cope EK Zhao KQ Vukovic K Kofonow JM Doghramji L González B Chiu AG Kennedy DW Palmer JN Leid JG Kreindler JL Cohen NA 《PloS one》2011,6(1):e15700
Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than non-smokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition. 相似文献
39.
An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination 总被引:1,自引:0,他引:1
Bauman Y Nachmani D Vitenshtein A Tsukerman P Drayman N Stern-Ginossar N Lankry D Gruda R Mandelboim O 《Cell host & microbe》2011,9(2):93-102
The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system. 相似文献
40.