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131.
Specific Binding of [11 C]Spiroperidol in Rat Brain In Vivo 总被引:2,自引:0,他引:2
Carroll D. Arnett Joanna S. Fowler Alfred P. Wolf Robert R. MacGregor 《Journal of neurochemistry》1983,40(2):455-459
Spiroperidol labeled with carbon-11, a short-lived positron-emitting radionuclide, was used to determine the time course of specific binding of this radioligand to the neuroleptic receptor in vivo in the rat. The three major bran pools--specifically bound, nonspecifically bound, and free (unbound)--were determined over a 60-mm time course by a rapid filtration technique, utilizing (-)- and (+)-butaclamol pretreatments to assess total and nonspecifically bound activities, respectively, in striatum and cerebellum. The ratio of specifically to nonspecifically bound pools in the striatum was 4.1 at 30 min and 5.1 at 60 min. Thus [11C]spiroperidol may be useful for labeling neuroleptic receptors in vivo for serial studies using positron emission transaxial tomography. 相似文献
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Irvin MR Wineinger NE Rice TK Pajewski NM Kabagambe EK Gu CC Pankow J North KE Wilk JB Freedman BI Franceschini N Broeckel U Tiwari HK Arnett DK 《PloS one》2011,6(8):e24052
African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10(-7)≤P≤1.1*10(-5)) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10(-6)). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10(-4)) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans. 相似文献
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Listeria monocytogenes is a facultative intracellular pathogen that infects a large diversity of host cells, including macrophages. To avoid the phagosome microbicidal environment, L. monocytogenes secretes a pore-forming toxin (listeriolysin O, LLO) that releases the bacterium into the cytoplasm. We hypothesized that the α-defensins (HNPs) and/or humanized θ-defensin (RC-1) peptides produced by human and non-human primate neutrophils, respectively, cooperate with macrophages to control L. monocytogenes infection. Our results establish that HNP-1 and RC-1 enable macrophages to control L. monocytogenes intracellular growth by inhibiting phagosomal escape, as a consequence, bacteria remain trapped in a LAMP-1-positive phagosome. Importantly, HNP-1 interaction with macrophages and RC-1 interaction with bacteria are required to prevent macrophage infection. In accordance with these results, RC-1 is a more potent anti-listerial peptide than HNP-1 and HNP-1 is acquired by macrophages and trafficked to the phagocytosed bacteria. Finally, HNP-1 and RC-1 antimicrobial activity is complemented by their ability to prevent LLO function through two mechanisms, blocking LLO-dependent perforation of macrophage membranes and the release of LLO from the bacteria. In conclusion, at the site of infection the cooperation between antimicrobial peptides, such as HNP-1, and macrophages likely plays a critical role in the innate immune defence against L. monocytogenes. 相似文献
136.
Mário C BarrosoJúnior Guilherme P Esteves Thiago P Nunes Lucia MG Silva Alvaro CD Faria Pedro L Melo 《Biomedical engineering online》2011,10(1):14
Introduction
A novel system that combines a compact mobile instrument and Internet communications is presented in this paper for remote evaluation of tremors. The system presents a high potential application in Parkinson's disease and connects to the Internet through a TCP/IP protocol. Tremor transduction is carried out by accelerometers, and the data processing, presentation and storage were obtained by a virtual instrument. The system supplies the peak frequency (fp), the amplitude (Afp) and power in this frequency (Pfp), the total power (Ptot), and the power in low (1-4 Hz) and high (4-7 Hz) frequencies (Plf and Phf, respectively). 相似文献137.
Ju-Sheng Zheng Donna K. Arnett Laurence D. Parnell Yu-Chi Lee Yiyi Ma Caren E. Smith Kris Richardson Duo Li Ingrid B. Borecki Katherine L. Tucker José M. Ordovás Chao-Qiang Lai 《PloS one》2013,8(6)
Background
Neighboring genes PIK3CA and KCNMB3 are both important for insulin signaling and β-cell function, but their associations with glucose-related traits are unclear.Objective
The objective was to examine associations of PIK3CA-KCNMB3 variants with glucose-related traits and potential interaction with dietary fat.Design
We first investigated genetic associations and their modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820). Nine single-nucleotide polymorphisms (SNPs) were selected for analysis, covering more than 80% of the SNPs in the region. We then sought to replicate the findings in the Boston Puerto Rican Health Study (BPRHS) (n = 844).Results
For KCNMB3 missense mutation rs7645550, meta-analysis indicated that homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in minor allele T homozygotes compared with major allele C carriers (pooled P-value = 0.004); for another SNP rs1183319, which is in moderate LD with rs7645550, minor allele G carriers had higher HOMA-IR compared with non-carriers in both populations (pooled P-value = 0.028). In GOLDN, rs7645550 T allele homozygotes had lower HOMA-IR only when dietary n-3: n-6 PUFA ratio was low (≤0.11, P = 0.001), but not when it was high (>0.11, P-interaction = 0.033). Similar interaction was observed between rs1183319 and n-3: n-6 PUFA ratio on HOMA-IR (P-interaction = 0.001) in GOLDN. Variance contribution analyses in GOLDN confirmed the genetic association and gene-diet interaction. In BPRHS, dietary n-3: n-6 PUFA ratio significantly modulated the association between rs1183319 and HbA1c (P-interaction = 0.034).Conclusion
PIK3CA-KCNMB3 variants are associated with insulin resistance in populations of different ancestries, and are modified by dietary PUFA. 相似文献138.
Edward B. Arnett Cris D. Hein Michael R. Schirmacher Manuela M. P. Huso Joseph M. Szewczak 《PloS one》2013,8(6)
Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21–51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities. 相似文献
139.
Linli Zhou Xiaoying Tian Cailei Zhu Fangwei Wang Jonathan MG Higgins 《EMBO reports》2014,15(3):273-281
Histone modifications coordinate the chromatin localization of key regulatory factors in mitosis. For example, mitotic phosphorylation of Histone H3 threonine‐3 (H3T3ph) by Haspin creates a binding site for the chromosomal passenger complex (CPC). However, how these histone modifications are spatiotemporally controlled during the cell cycle is unclear. Here we show that Plk1 binds to Haspin in a Cdk1‐phosphorylation‐dependent manner. Reducing Plk1 activity decreases the phosphorylation of Haspin and inhibits H3T3ph, particularly in prophase, suggesting that Plk1 is required for initial activation of Haspin in early mitosis. These studies demonstrate that Plk1 can positively regulate CPC recruitment in mitosis. 相似文献
140.
Frederique M Moret Kim MG van der Wurff-Jacobs Johannes WJ Bijlsma Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2014,16(6)