全文获取类型
收费全文 | 2724篇 |
免费 | 197篇 |
国内免费 | 119篇 |
专业分类
3040篇 |
出版年
2023年 | 21篇 |
2022年 | 57篇 |
2021年 | 105篇 |
2020年 | 72篇 |
2019年 | 90篇 |
2018年 | 101篇 |
2017年 | 73篇 |
2016年 | 86篇 |
2015年 | 159篇 |
2014年 | 158篇 |
2013年 | 218篇 |
2012年 | 225篇 |
2011年 | 180篇 |
2010年 | 128篇 |
2009年 | 103篇 |
2008年 | 95篇 |
2007年 | 112篇 |
2006年 | 104篇 |
2005年 | 106篇 |
2004年 | 105篇 |
2003年 | 80篇 |
2002年 | 55篇 |
2001年 | 64篇 |
2000年 | 55篇 |
1999年 | 55篇 |
1998年 | 28篇 |
1997年 | 26篇 |
1996年 | 23篇 |
1995年 | 28篇 |
1994年 | 27篇 |
1993年 | 19篇 |
1992年 | 39篇 |
1991年 | 30篇 |
1990年 | 18篇 |
1989年 | 22篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 15篇 |
1984年 | 17篇 |
1983年 | 17篇 |
1982年 | 14篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1971年 | 8篇 |
排序方式: 共有3040条查询结果,搜索用时 15 毫秒
991.
Guisheng Zhou Hanqing Pang Yuping Tang Xin Yao Xuan Mo Shaoqing Zhu Sheng Guo Dawei Qian Yefei Qian Shulan Su Li Zhang Chun Jin Yong Qin Jin-ao Duan 《Amino acids》2013,44(5):1293-1305
This work presented a new analytical methodology based on hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode for analysis of 24 underivatized free amino acids (FAAs) in functional foods. The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections and limit of quantifications, precision, repeatability, stability and recovery of all target compounds, and it was used to determine the nutritional substances of FAAs in ginkgo seeds and further elucidate the nutritional value of this functional food. The result showed that ginkgo seed turned out to be a good source of FAAs with high levels of several essential FAAs and to have a good nutritional value. Furthermore, the principal component analysis was performed to classify the ginkgo seed samples on the basis of 24 FAAs. As a result, the samples could be mainly clustered into three groups, which were similar to areas classification. Overall, the presented method would be useful for the investigation of amino acids in edible plants and agricultural products. 相似文献
992.
Steven T. Staben Nicole Blaquiere Vickie Tsui Aleksandr Kolesnikov Steven Do Erin K. Bradley Jenna Dotson Richard Goldsmith Timothy P. Heffron John Lesnick Cristina Lewis Jeremy Murray Jim Nonomiya Alan G. Olivero Jodie Pang Lionel Rouge Laurent Salphati BinQing Wei Ping Wu 《Bioorganic & medicinal chemistry letters》2013,23(3):897-901
Substructural class effects surrounding replacement of a ‘cis’ N-methyl aniline amide within potent and selective thienobenzoxepin PI3-kinase inhibitors are disclosed. While a simple aryl to alkyl switch was not tolerated due to differences in preferred amide conformation, heterocyclic amide isosteres with maintained aryl substitution improved potency and metabolic stability at the cost of physical properties. These gains in potency allowed lipophilic deconstruction of the arene to simple branched alkyl substituents. As such, overall lipophilicity-neutral, MW decreases were realized relative to the aniline amide series. The improved properties for lead compound 21 resulted in high permeability, solubility and bioavailability. 相似文献
993.
Brian S. Safina Zachary K. Sweeney Jun Li Bryan K. Chan Angelina Bisconte Diane Carrera Georgette Castanedo Michael Flagella Robert Heald Cristina Lewis Jeremy M. Murray Jim Nonomiya Jodie Pang Steve Price Karin Reif Laurent Salphati Eileen M. Seward Binqing Wei Daniel P. Sutherlin 《Bioorganic & medicinal chemistry letters》2013,23(17):4953-4959
In an effort to identify potent and isoform selective inhibitors of PI3Kδ, GNE-293 (34) was identified. Inhibitor 2 was found to induce micronuclei formation in both the MNT and HCA in vitro assays. Compounds testing negative for genotoxicity were successfully identified through modifications of the 2-benzimidazole substituent and the methylene moiety to disrupt planarity. A variety of heteroatom linkers were explored to examine their effect on potency and isoform selectivity by restricting torsional angles to favor ligand interactions with PI3Kδ’s Trp760. These modifications also resulted in an improved in vivo pharmacokinetic profile. 相似文献
994.
Lung cancer is an significant cause of death worldwide, and non–small-cell lung cancer (NSCLC) is the most common type of lung cancer. MicroRNAs (miRNAs) have been identified to play key roles in NSCLC development. Recently, it has been reported that miR-605-5p is a cancer-related miRNA in several types of tumors. In this study, we study the role of miR-605-5p in NSCLC cells. We find that miR-605-5p is upregulated in NSCLC cells. Overexpression of miR-605-5p significantly promotes lung cancer invasion and migration in H460 and H1299 cells. Besides this, miR-605-5p also promotes lung cancer cell carcinoma proliferation and metastasis in vivo. However, downregulation of miR-605-5p inhibits cell invasion and migration by inhibiting lung cancer cell carcinoma proliferation and metastasis. In addition, the luciferase report assay identifies 3′-untranslated region tumor necrosis factor α-induced protein 3 (TNFAIP3) as a target of miR-605-5p. Silencing of TNFAIP3 promotes invasion and proliferation in lung cancer. In addition, the knockdown of TNFAIP3 restores the significant decrease in invasion and proliferation in miR-605-5p-inhibitor–transfected lung cancer cells. In conclusion, miR-605-5p promotes invasion and proliferation by targeting TNFAIP3 in NSCLC, and may provide possible biomarkers for NSCLC therapy. 相似文献
995.
Rana K Fam BC Clarke MV Pang TP Zajac JD MacLean HE 《American journal of physiology. Endocrinology and metabolism》2011,301(5):E767-E778
In men, as testosterone levels decrease, fat mass increases and muscle mass decreases. Increased fat mass in men, in particular central obesity, is a major risk factor for type 2 diabetes, cardiovascular disease, and all-cause mortality. Testosterone treatment has been shown to decrease fat mass and increase fat-free mass. We hypothesize that androgens act directly via the DNA binding-dependent actions of the androgen receptor (AR) to regulate genes controlling fat mass and metabolism. The aim of this study was to determine the effect of a global DNA binding-dependent (DBD) AR knockout (DBD-ARKO) on the metabolic phenotype in male mice by measuring body mass, fat mass, food intake, voluntary physical activity, resting energy expenditure, substrate oxidation rates, serum glucose, insulin, lipid, and hormone levels, and metabolic gene expression levels and second messenger protein levels. DBD-ARKO males have increased adiposity despite a decreased total body mass compared with wild-type (WT) males. DBD-ARKO males showed reduced voluntary activity, decreased food intake, increased serum leptin and adiponectin levels, an altered lipid metabolism gene profile, and increased phosphorylated CREB levels compared with WT males. This study demonstrates that androgens acting via the DNA binding-dependent actions of the AR regulate fat mass and metabolism in males and that the increased adiposity in DBD-ARKO male mice is associated with decreased voluntary activity, hyperleptinemia and hyperadiponectinemia and not with insulin resistance, increased food intake, or decreased resting energy expenditure. 相似文献
996.
Responses in the physiology and biochemistry of Korean pine (Pinus koraiensis) under supplementary UV-B radiation 总被引:1,自引:0,他引:1
The effect of supplementary UV-B radiation on Korean pine (Pinus koraiensis Sieb. et Zucc) was investigated. Compared with the control, the T1, T2, and T3 UV-B treatments increased by 1.40, 2.81, and 4.22 kJ m?2 d?1, respectively. Gas-exchange parameters, photosynthetic pigment concentrations, contents of secondary metabolites, epicuticular wax, free radical, malondialdehyde (MDA), and the activities of antioxidant enzymes were determined after 40 d of exposure. The concentrations of chlorophyll (Chl) a, Chl b, total Chl, carotenoid (Car), and the ratio Chl a/b in the pine needles were in the following order: T1 > T2 > T3. Compared with the control, the contents of flavonoids and epicuticular wax significantly decreased in all levels of supplementary UV-B radiations (p<0.05). Moreover, the contents of hydrogen peroxide (H2O2) and MDA significantly increased with the enhanced UV-B radiations (p<0.05). Korean pine can increase the catalase, ascorbate peroxidase, and superoxide dismutase activities to prevent oxidative stress by supplementary UV-B radiation. However, its defence mechanism is not efficient enough to prevent UV-Binduced damage. 相似文献
997.
Wangping Yue Xingtang Fang Chunlei Zhang Yonghong Pang Haixia Xu Chuanwen Gu Ruying Shao Chuzhao Lei Hong Chen 《Molecular biology reports》2011,38(5):2927-2932
The ATP-binding cassette transporter ABCG2 (also known as breast cancer resistance protein, BCRP) belongs to the ATP-binding cassette (ABC) family of transmembrane drug transporters, playing a crucial role in the protection
of various cells and tissues against xenotoxins and/or endotoxins. Recently, several studies have proposed it as the potential
gene underlying the QTL on bovine chromosome 6. Hence, in this study, the PCR-SSCP method was applied to detect two polymorphisms
(A → C and A → G) in the target sequence coding nucleotide-binding domain (NBD) region of ABCG2 and evaluate its associations with milk production traits and mastitis-related traits among Chinese Holsteins. In the analyzed
population, the allelic frequencies for the A and B alleles were 0.5990 and 0.4010, respectively and the genotypic frequencies
were in Hardy–Weinberg disequilibrium (P < 0.01). Moreover, significant statistical relationships between the polymorphisms of ABCG2 gene and following traits, including milk yields, milk protein percentage and somatic cell scores (SCS), were found (P < 0.05). When compared with AA genotype, BB genotype was associated with higher milk yields during 1st and 2nd lactations,
as well as lower milk protein percentage and SCS. Thus, BB genotype is suggested to be a molecular marker for superior milk
performance. 相似文献
998.
Abiramy Krishnan Siti Aisyah Alias Clemente Michael Vui Ling Wong Ka-Lai Pang Peter Convey 《Polar Biology》2011,34(10):1535-1542
Various microbial groups are well known to produce a range of extracellular enzymes and other secondary metabolites. However,
the occurrence and importance of investment in such activities have received relatively limited attention in studies of Antarctic
soil microbiota. In order to examine extracellular enzyme production in this chronically low-temperature environment, fungi
were isolated from ornithogenic, pristine and human-impacted soils collected from the Fildes Peninsula, King George Island,
Antarctica during the austral summer in February 2007. Twenty-eight isolates of psychrophilic and psychrotolerant fungi were
obtained and screened at a culture temperature of 4°C for activity of extracellular hydrolase enzymes (amylase, cellulase,
protease), using R2A agar plates supplemented with (a) starch for amylase activity, (b) carboxymethyl cellulose and trypan
blue for cellulase activity or (c) skim milk for protease activity. Sixteen isolates showed activity for amylase, 23 for cellulase
and 21 for protease. One isolate showed significant activity across all three enzyme types, and a further 10 isolates showed
significant activity for at least two of the enzymes. No clear associations were apparent between the fungal taxa isolated
and the type of source soil, or in the balance of production of different extracellular enzymes between the different soil
habitats sampled. Investment in extracellular enzyme production is clearly an important element of the survival strategy of
these fungi in maritime Antarctic soils. 相似文献
999.
Chiu Tsai-Hsin Pang Jen-Chieh Chen Ming-Hui Tsen Hau-Yang 《World journal of microbiology & biotechnology》2011,27(2):465-469
Salmonella enterica serovar Choleraesuis (S.
Choleraesuis) can cause salmonellosis in pigs and humans. Currently, the most common method used for the subtyping of this Salmonella serovar is pulsed field gel electrophoresis (PFGE) using XbaI as a DNA digestion enzyme. In this study, we compared and combined PFGE with the randomly amplified polymorphic DNA method,
for the typing of 95 S. Choloraesuis strains isolated from diseased pigs. Using PFGE with XbaI, with AvrII, and with SpeI digested DNA, 29, 74, and 40 patterns, respectively, were obtained. Also, 53, 15, and 35 strains, respectively, belong to
the major patterns X1, A1, and S1. When these three digestion patterns were combined, 83 PFGE pattern combinations were obtained.
On the other hand, using RAPD with selected primer alone generated 76 patterns, and 11 strains which fell within a single
X1A1S1 PFGE combination pattern were discriminated into 10 patterns. Thus, for S. Choloraesuis, PFGE with AvrII allowed higher discrimination than PFGE with XbaI, and some of the PFGE groupings obtained by combining the XbaI, AvrII and SpeI digestion patterns were further subdivided by the RAPD method. 相似文献
1000.
Miller MC Ribeiro JP Roldós V Martín-Santamaría S Cañada FJ Nesmelova IA André S Pang M Klyosov AA Baum LG Jiménez-Barbero J Gabius HJ Mayo KH 《Glycobiology》2011,21(12):1627-1641
By definition, adhesion/growth-regulatory galectins are known for their ability to bind β-galactosides such as Galβ(1 → 4)Glc (lactose). Indications for affinity of human galectin-1 to α-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-π stacking. These issues are resolved by a combination of (15)N-(1)H heteronuclear single quantum coherence (HSQC) chemical shift and saturation transfer difference nuclear magnetic resonance (STD NMR) epitope mappings with docking analysis, using the α(1 → 3/4)-linked digalactosides and also Galα(1 → 6)Glc (melibiose) as test compounds. The experimental part revealed interaction with the canonical lectin site, and this preferentially via the non-reducing-end galactose moiety. Low-energy conformers appear to be selected without notable distortion, as shown by molecular dynamics simulations. With the α(1 → 4) disaccharide, however, the typical CH-π interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of α-linkage in digalactosides has an impact on maintaining CH-π interactions and the pattern of hydrogen bonding, explaining preference for the α(1 → 3) linkage. Thus, this lectin is able to accommodate both α- and β-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit. 相似文献