全文获取类型
收费全文 | 35091篇 |
免费 | 2859篇 |
国内免费 | 1894篇 |
专业分类
39844篇 |
出版年
2024年 | 68篇 |
2023年 | 390篇 |
2022年 | 942篇 |
2021年 | 1642篇 |
2020年 | 1038篇 |
2019年 | 1256篇 |
2018年 | 1232篇 |
2017年 | 865篇 |
2016年 | 1328篇 |
2015年 | 2033篇 |
2014年 | 2371篇 |
2013年 | 2558篇 |
2012年 | 3093篇 |
2011年 | 2775篇 |
2010年 | 1725篇 |
2009年 | 1432篇 |
2008年 | 1669篇 |
2007年 | 1516篇 |
2006年 | 1356篇 |
2005年 | 1143篇 |
2004年 | 1019篇 |
2003年 | 870篇 |
2002年 | 747篇 |
2001年 | 679篇 |
2000年 | 684篇 |
1999年 | 657篇 |
1998年 | 388篇 |
1997年 | 336篇 |
1996年 | 360篇 |
1995年 | 334篇 |
1994年 | 326篇 |
1993年 | 216篇 |
1992年 | 352篇 |
1991年 | 270篇 |
1990年 | 306篇 |
1989年 | 257篇 |
1988年 | 189篇 |
1987年 | 172篇 |
1986年 | 152篇 |
1985年 | 135篇 |
1984年 | 121篇 |
1983年 | 95篇 |
1982年 | 77篇 |
1981年 | 61篇 |
1979年 | 75篇 |
1978年 | 55篇 |
1977年 | 53篇 |
1975年 | 59篇 |
1974年 | 47篇 |
1973年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 8 毫秒
991.
Li J Zhao GZ Huang HY Qin S Zhu WY Zhao LX Xu LH Zhang S Li WJ Strobel G 《Antonie van Leeuwenhoek》2012,101(3):515-527
Endophytic actinobacteria isolated from Artemisia annua were characterized and evaluated for their bioactivities. A total of 228 isolates representing at least 19 different genera
of actinobacteria were obtained and several of them seemed to be novel taxa. An evaluation of antimicrobial activity showed
that more isolates possessed activity towards plant pathogens than activity against other pathogenic bacteria or yeasts. High
frequencies of PCR amplification were obtained for type I polyketide synthases (PKS-I, 21.1%), type II polyketide synthases
(PKS-II, 45.2%) and nonribosomal peptide synthetases (NRPS, 32.5%). The results of herbicidal activity screening indicated
that 19 out of 117 samples of fermentation broths completely inhibited the germination of Echinochloa crusgalli. This study indicated that endophytic actinobacteria associated with A. annua are abundant and have potentially beneficial and diverse bioactivities which should be pursued for their biotechnical promise. 相似文献
992.
993.
994.
Li Q Huang XJ He W Ding J Jia JT Fu G Wang HX Guo LJ 《Cellular and molecular neurobiology》2009,29(2):169-180
We previously reported that inhibition of Rho-kinase (ROCK) by hydroxyl fasudil improves cognitive deficit and neuronal damage
in rats with chronic cerebral ischemia (Huang et al., Cell Mol Neurobiol 28:757–768, 2008). In this study, fasudil mesylate
(FM) was investigated for its neuroprotective potential in rats with ischemia following middle cerebral artery occlusion (MCAO)
and reperfusion. The effect of fasudil mesylate was also studied in rat brain cortical and hippocampal slices treated with
oxygen-glucose deprivation (OGD) injury. Gross anatomy showed that cerebral infarct size, measured with 2,3,5-triphenyltetrazolium
chloride (TTC) staining, was significantly smaller in the FM-treated than in the non-FM-treated ischemic rats. In the brain
regions vulnerable to ischemia of ischemic rats, fasudil mesylate was also found to significantly restore the enzyme protein
expression level of endothelial nitric oxide synthase (eNOS), which was decreased in ischemia. However, it remarkably reduced
the protein synthesis of inducible nitric oxide synthase (iNOS) that was induced by ischemia and reperfusion. In rat brain
slices treated with OGD injury, fasudil mesylate increased the neuronal cell viability by 40% for cortex and by 61% for hippocampus,
respectively. Finally, in the presence of OGD and fasudil mesylate, superoxide dismutase (SOD) activity was increased by 50%
for cortex and by 58% for hippocampus, compared to OGD only group. In conclusion, our in vivo study showed that fasudil mesylate
not only decreased neurological deficit but also reduced cerebral infarct size, possibly and at least partially by augmenting
eNOS protein expression and inhibiting iNOS protein expression after ischemia-reperfusion.
Xian-Ju Huang contributed equally to this article. 相似文献
995.
Y C Huang B N Wu J L Yeh S J Chen J C Liang Y C Lo I J Chen 《Bioorganic & medicinal chemistry》2001,9(7):1739-1746
A series of vanilloid-type beta-adrenoceptor blockers derived from antioxidant traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant beta-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vivo tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent beta-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional alpha-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. The antioxidant activity may be due to their alpha and beta unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine. 相似文献
996.
Xu D Huang W Li Y Wang H Huang H Cui X 《The Plant journal : for cell and molecular biology》2012,69(5):792-808
The mitotic cell cycle in higher eukaryotes is of pivotal importance for organ growth and development. Here, we report that Elongator, an evolutionarily conserved histone acetyltransferase complex, acts as an important regulator of mitotic cell cycle to promote leaf patterning in Arabidopsis. Mutations in genes encoding Elongator subunits resulted in aberrant cell cycle progression, and the altered cell division affects leaf polarity formation. The defective cell cycle progression is caused by aberrant DNA replication and increased DNA damage, which activate the DNA replication checkpoint to arrest the cell cycle. Elongator interacts with proliferating cell nuclear antigen (PCNA) and is required for efficient histone 3 (H3) and H4 acetylation coupled with DNA replication. Levels of chromatin-bound H3K56Ac and H4K5Ac known to associate with replicons during DNA replication were reduced in the mutants of both Elongator and chromatin assembly factor 1 (CAF-1), another protein complex that physically interacts with PCNA for DNA replication-coupled chromatin assembly. Disruptions of CAF-1 also led to severe leaf polarity defects, which indicated that Elongator and CAF-1 act, at least partially, in the same pathway to promote cell cycle progression. Collectively, our results demonstrate that Elongator is an important regulator of mitotic cell cycle, and the Elongator pathway plays critical roles in promoting leaf polarity formation. 相似文献
997.
Kuen-Feng Chen Kuan-Chuan Pao Jung-Chen Su Yi-Chieh Chou Chun-Yu Liu Hui-Ju Chen Jui-Wen Huang InKi Kim Chung-Wai Shiau 《Bioorganic & medicinal chemistry》2012,20(20):6144-6153
Cancerous inhibitor of PP2A (CIP2A) is a novel human oncoprotein that inhibits PP2A, contributing to tumor aggressiveness in various cancers. Several studies have shown that downregulation of CIP2A by small molecules reduces PP2A-dependent phosphorylation of Akt and induces cell death. Here, a series of mono- and di-substituted quinazoline and pyrimidine derivatives based on the skeleton of erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against hepatocellular carcinoma were evaluated. The di-substituted quinazoline and pyrimidine derivatives were more potent inhibitors of cancer-cell proliferation than the mono-substituted derivatives. In particular, compound 1 with chloride at position 2 of quinazoline was as potent as erlotinib in inducing cell death but no inhibition for EGFR activity. Further assays confirmed a correlation between cell death, and CIP2A and Akt inhibition by these derivatives. Among all the derivatives, compounds 19 and 22 showed the most potent antiproliferative activities and the strongest inhibition of CIP2A and p-Akt expression. 相似文献
998.
Background
We have previously shown that modafinil promotes wakefulness via dopamine receptor D1 and D2 receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc) that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal.Methodology/Principal Findings
In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil.Conclusions/Significance
These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil. 相似文献999.
Shalabh Dixit B. Emma Huang Ma. Teresa Sta Cruz Paul T. Maturan Jhon Christian E. Ontoy Arvind Kumar 《PloS one》2014,9(10)
Background
The coupling of biotic and abiotic stresses leads to high yield losses in rainfed rice (Oryza sativa L.) growing areas. While several studies target these stresses independently, breeding strategies to combat multiple stresses seldom exist. This study reports an integrated strategy that combines QTL mapping and phenotypic selection to develop rice lines with high grain yield (GY) under drought stress and non-stress conditions, and tolerance of rice blast.Methodology
A blast-tolerant BC2F3-derived population was developed from the cross of tropical japonica cultivar Moroberekan (blast- and drought-tolerant) and high-yielding indica variety Swarna (blast- and drought-susceptible) through phenotypic selection for blast tolerance at the BC2F2 generation. The population was studied for segregation distortion patterns and QTLs for GY under drought were identified along with study of epistatic interactions for the trait.Results
Segregation distortion, in favour of Moroberekan, was observed at 50 of the 59 loci. Majority of these marker loci co-localized with known QTLs for blast tolerance or NBS-LRR disease resistance genes. Despite the presence of segregation distortion, high variation for DTF, PH and GY was observed and several QTLs were identified under drought stress and non-stress conditions for the three traits. Epistatic interactions were also detected for GY which explained a large proportion of phenotypic variance observed in the population.Conclusions
This strategy allowed us to identify QTLs for GY along with rapid development of high-yielding purelines tolerant to blast and drought with considerably reduced efforts. Apart from this, it also allowed us to study the effects of the selection cycle for blast tolerance. The developed lines were screened at IRRI and in the target environment, and drought and blast tolerant lines with high yield were identified. With tolerance to two major stresses and high yield potential, these lines may provide yield stability in rainfed rice areas. 相似文献1000.
David J. Rosenman Yao‐ming Huang Ke Xia Keith Fraser Victoria E. Jones Colleen M. Lamberson Patrick Van Roey Wilfredo Colón Christopher Bystroff 《Protein science : a publication of the Protein Society》2014,23(4):400-410
Wild‐type green fluorescent protein (GFP) folds on a time scale of minutes. The slow step in folding is a cis–trans peptide bond isomerization. The only conserved cis‐peptide bond in the native GFP structure, at P89, was remodeled by the insertion of two residues, followed by iterative energy minimization and side chain design. The engineered GFP was synthesized and found to fold faster and more efficiently than its template protein, recovering 50% more of its fluorescence upon refolding. The slow phase of folding is faster and smaller in amplitude, and hysteresis in refolding has been eliminated. The elimination of a previously reported kinetically trapped state in refolding suggests that X‐P89 is trans in the trapped state. A 2.55 Å resolution crystal structure revealed that the new variant contains only trans‐peptide bonds, as designed. This is the first instance of a computationally remodeled fluorescent protein that folds faster and more efficiently than wild type. 相似文献