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901.
Cao P Wang QJ Zhu XT Zhou H Li R Wang WP 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(7-8):527-532
Quantitative determination of the allele frequency of single-nucleotide polymorphism (SNP) in pooled DNA samples is a promising approach to clarify the relationships between SNPs and diseases. Here, we present such a simple, accurate, and inexpensive method for quantitative determining the allele frequency in pooled DNA samples. Three steps of DNA pooling, PCR amplification and sequencing are involved in this assay. Although direct determination of the allele frequency from the two allele-specific fluorescence intensities is possible, correction for differential response of alleles is important. We explored the effect of differential response of alleles on test statistics and provide a solution to this problem based on heterozygous fluorescence intensities. We demonstrate the accuracy and reliability of this assay on pooled DNA samples with pre-determined allele frequencies from 7.1% to 53.9%. The accuracy of allele frequency measurements is high, with a correlation coefficient of r2 = 0.997 between measured and known frequencies. We believe that by providing a means for SNP genotyping up to hundreds of samples simultaneously, inexpensively, and reproducibly, this method is a powerful strategy for detecting meaningful polymorphic differences in candidate gene association studies. 相似文献
902.
Human P450 protein CYP2C9 is one of the major drug-metabolizing isomers, contributing to the oxidation of 16% of the drugs
currently in clinical use. To examine the interaction mechanisms between CYP2C9 and proton pump inhibitions (PPIs), we used
molecular docking and molecular dynamics (MD) simulation methods to investigate the conformations and interactions around
the binding sites of PPIs/CYPP2C9. Results from molecular docking and MD simulations demonstrate that nine PPIs adopt two
different conformations (extended and U-bend structures) at the binding sites and position themselves far above the heme of
2C9. The presence of PPIs changes the secondary structures and residue flexibilities of 2C9. Interestingly, at the binding
sites of all PPI–CYP2C9 complexes except for Lan/CYP2C9, there are hydrogen-bonding networks made of PPIs, water molecules,
and some residues of 2C9. Moreover, there are strong hydrophobic interactions at all binding sites for PPIs/2C9, which indicate
that electrostatic interactions and hydrophobic interactions appear to be important for stabilizing the binding sites of most
PPIs/2C9. However, in the case of Lan/2C9, the hydrophobic interactions are more important than the electrostatic interactions
for stabilizing the binding site. In addition, an interesting conformational conversion from extended to U-bend structures
was observed for pantoprazole, which is attributed to an H-bond interaction in the binding pocket, an internal π–π stacking
interaction, and an internal electrostatic interaction of pantoprazole. 相似文献
903.
Structural colors are generated by scattering of light by variations in tissue nanostructure. They are widespread among animals and have been studied most extensively in butterflies and moths (Lepidoptera), which exhibit the widest diversity of photonic nanostructures, resultant colors, and visual effects of any extant organism. The evolution of structural coloration in lepidopterans, however, is poorly understood. Existing hypotheses based on phylogenetic and/or structural data are controversial and do not incorporate data from fossils. Here we report the first example of structurally colored scales in fossil lepidopterans; specimens are from the 47-million-year-old Messel oil shale (Germany). The preserved colors are generated by a multilayer reflector comprised of a stack of perforated laminae in the scale lumen; differently colored scales differ in their ultrastructure. The original colors were altered during fossilization but are reconstructed based upon preserved ultrastructural detail. The dorsal surface of the forewings was a yellow-green color that probably served as a dual-purpose defensive signal, i.e. aposematic during feeding and cryptic at rest. This visual signal was enhanced by suppression of iridescence (change in hue with viewing angle) achieved via two separate optical mechanisms: extensive perforation, and concave distortion, of the multilayer reflector. The fossils provide the first evidence, to our knowledge, for the function of structural color in fossils and demonstrate the feasibility of reconstructing color in non-metallic lepidopteran fossils. Plastic scale developmental processes and complex optical mechanisms for interspecific signaling had clearly evolved in lepidopterans by the mid-Eocene. 相似文献
904.
Living in an enriched environment with complex physical and social stimulation leads to improved cognitive and metabolic health. In white fat, enrichment induced the upregulation of the brown fat cell fate determining gene Prdm16, brown fat-specific markers, and genes involved in thermogenesis and β-adrenergic signaling. Moreover, pockets of cells with prototypical brown fat morphology and high UCP1 levels were observed in the white fat of enriched mice associated with resistance to diet-induced obesity. Hypothalamic overexpression of BDNF reproduced the enrichment-associated activation of the brown fat gene program and lean phenotype. Inhibition of BDNF signaling by genetic knockout or dominant-negative trkB reversed this phenotype. Our genetic and pharmacologic data suggest a mechanism whereby induction of hypothalamic BDNF expression in response to environmental stimuli leads to selective sympathoneural modulation of white fat to induce "browning" and increased energy dissipation. 相似文献
905.
Junjie Xiao Huaming Cao Dandan Liang Ying Liu Hong Zhang Hong Zhao Yi Liu Jun Li Biao Yan Luying Peng Zhaonian Zhou Yi‐Han Chen 《Journal of cellular and molecular medicine》2011,15(5):1166-1176
Microtubule integrity is important in cardio‐protection, and microtubule disruption has been implicated in the response to ischemia in cardiac myocytes. However, the effects of Taxol, a common microtubule stabilizer, are still unknown in ischemic ventricular arrhythmias. The arrhythmia model was established in isolated rat hearts by regional ischemia, and myocardial infarction model by ischemia/reperfusion. Microtubule structure was immunohistochemically measured. The potential mechanisms were studied by measuring reactive oxygen species (ROS), activities of oxidative enzymes, intracellular calcium concentration ([Ca2+]i) and Ca2+ transients by using fluorometric determination, spectrophotometric assays and Fura‐2‐AM and Fluo‐3‐AM, respectively. The expression and activity of sarcoplasmic reticulum Ca2+‐ATPase (SERCA2a) was also examined using real‐time polymerase chain reaction, Western blot and pyruvate/Nicotinamide adenine dinucleotide‐coupled reaction. Our data showed that Taxol (0.1, 0.3 and 1 μM) effectively reduced the number of ventricular premature beats and the incidence and duration of ventricular tachycardia. The infarct size was also significantly reduced by Taxol (1 μM). At the same time, Taxol preserved the microtubule structure, increased the activity of mitochondrial electron transport chain complexes I and III, reduced ROS levels, decreased the rise in [Ca2+]i and preserved the amplitude and decay times of Ca2+ transients during ischemia. In addition, SERCA2a activity was preserved by Taxol during ischemia. In summary, Taxol prevents ischemic ventricular arrhythmias likely through ameliorating abnormal calcium homeostasis and decreasing the level of ROS. This study presents evidence that Taxol may be a potential novel therapy for ischemic ventricular arrhythmias. 相似文献
906.
Li Y Zheng H Luo R Wu H Zhu H Li R Cao H Wu B Huang S Shao H Ma H Zhang F Feng S Zhang W Du H Tian G Li J Zhang X Li S Bolund L Kristiansen K de Smith AJ Blakemore AI Coin LJ Yang H Wang J Wang J 《Nature biotechnology》2011,29(8):723-730
Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation. 相似文献
907.
To investigate the expression and biological significance of Leptin, Leptin receptor, Vascular Endothelial Growth Factor (VEGF),
and CD34 protein in colorectal carcinoma tissues. The expression of Leptin, Leptin receptor, VEGF, and CD34 was detected in
68 cases of colorectal carcinoma tissues, paired para-carcinoma tissues and normal colorectal tissues by Immunohistochemical
SP Method. The results and related clinicopathological data were analyzed. The positive rate of Leptin, Leptin receptor, and
VEGF was significantly higher in colorectal carcinoma tissues than that in paired para-carcinoma tissues and normal colorectal
tissues. The expression of Leptin, Leptin receptor, and VEGF was correlated with grade of tumor differentiation, depth of
bowel wall invasion, lymph node metastasis, Dukes stage, distant metastasis, and lympho/vascular tumor embolization. Microvessel
density (MVD) value in colorectal carcinoma was significantly higher than that in para-carcinoma tissues and normal colorectal
tissues, and the density in para-carcinoma tissues was higher than that in normal colorectal tissues. The expression of Leptin,
Leptin receptor, VEGF, and MVD value in colorectal carcinoma was positively correlated. In conclusion, microvessel density
value is an important index of the growth, invasion, and metastasis of colorectal carcinoma. The binding of Leptin and Leptin
receptor promotes the proliferation of colorectal carcinoma cells. The synergy between Leptin and VEGF accelerates the angiogenesis
in colorectal carcinoma and accelerates the invasion and metastasis of the tumor cells. 相似文献
908.
Choksi S Lin Y Pobezinskaya Y Chen L Park C Morgan M Li T Jitkaew S Cao X Kim YS Kim HS Levitt P Shih G Birre M Deng CX Liu ZG 《Molecular cell》2011,42(5):597-609
The regulation of apoptosis is critical for controlling tissue homeostasis and preventing tumor formation and growth. Reactive oxygen species (ROS) generation plays a key role in such regulation. Here, we describe a HIF-1 target, Vasn/ATIA (anti-TNFα-induced apoptosis), which protects cells against TNFα- and hypoxia-induced apoptosis. Through the generation of ATIA knockout mice, we show that ATIA protects cells from apoptosis through regulating the function of the mitochondrial antioxidant, thioredoxin-2, and ROS generation. ATIA is highly expressed in human glioblastoma, and ATIA knockdown in glioblastoma cells renders them sensitive to hypoxia-induced apoptosis. Therefore, ATIA is not only a HIF-1 target that regulates mitochondrial redox pathways but also a potentially diagnostic marker and therapeutic target in human glioblastoma. 相似文献
909.
910.
Youshuang Zhu Haibo Zhang Mingle Cao Zhenzhen Wei Feng Huang Peiji Gao 《Biotechnology and Bioprocess Engineering》2011,16(5):1027-1035
Production of laccase using a submerged culture of Trametes versicolor sdu-4 was optimized using a central composite design of the Response Surface Methodology. Optimized conditions gave a laccase
yield of 4,213 U/L which was approximately three times of that in basal medium. The laccase was purified to homogeneity using
a three-step process. The overall yield of the purification was 58%, with a purification fold of 11.4 and a specific activity
of 1320.7 U/mg protein. The molecular mass of the laccase was 60 kDa. The optimum pH values of the enzyme were 2.2, 3.7, and
7 for the oxidations of ABTS, DMP, and syringaldazine, respectively. The enzyme had adaptability to a broad pH range and high
temperature and wsa stable at pH 3.0 ∼ 10.0. The half-life of this laccase at 70°C was 2.2 h. Methyl red, 2-bromophenol, and
4-bromophenol were oxidized by the purified laccase in the absence of mediators. Purified laccase was effective in the decolorization
of several dyes and was not inhibited by Cu2+, Mn2+, Zn2+, Na+, K+, Mg2+, Ba2+, and Ca2+ at 5 mM. These excellent characteristics made it a highly attractive candidate for industrial use. 相似文献