全文获取类型
收费全文 | 37878篇 |
免费 | 3154篇 |
国内免费 | 2753篇 |
出版年
2024年 | 14篇 |
2023年 | 437篇 |
2022年 | 523篇 |
2021年 | 1930篇 |
2020年 | 1355篇 |
2019年 | 1711篇 |
2018年 | 1722篇 |
2017年 | 1174篇 |
2016年 | 1642篇 |
2015年 | 2401篇 |
2014年 | 2827篇 |
2013年 | 3074篇 |
2012年 | 3575篇 |
2011年 | 3165篇 |
2010年 | 1987篇 |
2009年 | 1614篇 |
2008年 | 1968篇 |
2007年 | 1718篇 |
2006年 | 1586篇 |
2005年 | 1285篇 |
2004年 | 1052篇 |
2003年 | 909篇 |
2002年 | 758篇 |
2001年 | 664篇 |
2000年 | 587篇 |
1999年 | 622篇 |
1998年 | 343篇 |
1997年 | 357篇 |
1996年 | 336篇 |
1995年 | 317篇 |
1994年 | 332篇 |
1993年 | 263篇 |
1992年 | 311篇 |
1991年 | 241篇 |
1990年 | 213篇 |
1989年 | 189篇 |
1988年 | 127篇 |
1987年 | 101篇 |
1986年 | 92篇 |
1985年 | 86篇 |
1984年 | 59篇 |
1983年 | 53篇 |
1982年 | 34篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1976年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 28 毫秒
31.
Mary T. Doan Michael D. Neinast Erika L. Varner Kenneth C. Bedi David Bartee Helen Jiang Sophie Trefely Peining Xu Jay P. Singh Cholsoon Jang J. Eduardo Rame Donita C. Brady Jordan L. Meier Kenneth B. Marguiles Zoltan Arany Nathaniel W. Snyder 《Journal of lipid research》2022,63(6):100224
Anabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of 13C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate. 相似文献
32.
Gao-Min Liu Wen-Xuan Xie Cai-Yun Zhang Ji-Wei Xu 《Journal of cellular physiology》2020,235(2):1624-1636
While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas—Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC. 相似文献
33.
Yibao Ma Yuanxi Xu Bryan D. Yestrepsky Roderick J. Sorenson Meng Chen Scott D. Larsen Hongmin Sun 《PloS one》2012,7(10)
Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of anti-virulence compounds could be a starting point for development of novel anti-microbial agents against S. aureus. 相似文献
34.
Fei Mi Ying Zhang Dan Yang Xiaozhao Tang Pengfei Wang Xiaoxia He Yunrun Zhang Jianyong Dong Yang Cao Chunli Liu Ke-Qin Zhang Jianping Xu 《PloS one》2016,11(2)
During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China. 相似文献
35.
Jinjin Shao Zhifei Xu Xueming Peng Min Chen Yuanrun Zhu Li Xu Hong Zhu Bo Yang Peihua Luo Qiaojun He 《PloS one》2016,11(1)
Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin–proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC. 相似文献
36.
The garlic stalk is a byproduct of garlic production and normally abandoned or burned, both of which cause environmental pollution. It is therefore appropriate to determine the conditions of efficient decomposition, and equally appropriate to determine the impact of this decomposition on soil properties. In this study, the soil properties, enzyme activities and nutrient dynamics associated with the decomposition of garlic stalk at different temperatures, concentrations and durations were investigated. Stalk decomposition significantly increased the values of soil pH and electrical conductivity. In addition, total nitrogen and organic carbon concentration were significantly increased by decomposing stalks at 40°C, with a 5∶100 ratio and for 10 or 60 days. The highest activities of sucrase, urease and alkaline phosphatase in soil were detected when stalk decomposition was performed at the lowest temperature (10°C), highest concentration (5∶100), and shortest duration (10 or 20 days). The evidence presented here suggests that garlic stalk decomposition improves the quality of soil by altering the value of soil pH and electrical conductivity and by changing nutrient dynamics and soil enzyme activity, compared to the soil decomposition without garlic stalks. 相似文献
37.
Yao-Song Gui Lianmei Wang Xinlun Tian Ruie Feng Aiping Ma Baiqiang Cai Hongbing Zhang Kai-Feng Xu 《PloS one》2012,7(9)
Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ERT2 mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ERT2) is under the control of the human surfactant protein C (SPC) promoter. The specificity and efficiency of Cre-ERT2 activity was first evaluated by crossing SPC-Cre-ERT2 mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ERT2 was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ERT2/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ERT2 in a mouse strain bearing TSC1 conditional knockout alleles (TSC1fx/fx). TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ERT2/TSC1fx/fx mice. Therefore this SPC-Cre-ERT2 mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease. 相似文献
38.
Arsenite efflux is not enhanced in the arsenate-tolerant phenotype of Holcus lanatus 总被引:1,自引:0,他引:1
B. Logoteta X. Y. Xu M. R. Macnair S. P. McGrath F. J. Zhao 《The New phytologist》2009,183(2):340-348
39.
40.
Yihe Lu Bojie Fu Liding Chen Zhiyun Ouyang Jianying Xu 《Biodiversity and Conservation》2006,15(8):2813-2827
Resolving the conflicts between biodiversity conservation and socioeconomic development is a global pursuit for the long-run
prospects of the human species. Based on Wenchuan County, a typical county in southwestern China, a group of 20 indicators
quantifying regional biodiversity and socioeconomic development was established to classify and evaluate the county area spatially.
A fuzzy c-means clustering (FCM) algorithm was used as the classification method. Three indices including BD, DL and DR characterizing
the value of biodiversity, the level and rate of socioeconomic development of the delineated regions were formulated. The
results indicated that Wenchuan County was optimally classified into 4 types of regions (region I to IV). The area percentages
of the regions vary widely from 4.3 to 65.7%. The sequences of the regions on biodiversity, socioeconomic development level,
and socioeconomic development rate were, respectively, IV > II > III > I, I > III > II > IV and III >I >II >IV. The spatial
strategy on coordinating biodiversity conservation and regional development is to develop mainly from the east(I, II, III)
and to conserve mainly in the west(IV). Eco-industry, such as eco-tourism and eco-agriculture, need to be emphasized in the
process of regional development. The quantitative methods used here may have a wide applicability. 相似文献