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991.
The last few years have witnessed the addition of new techniques and research strategies to the study of the population history of Arctic peoples. Osteon-photon analysis of bone cores provides an improved method of assigning age at death to skeletons. Consequently, it is possible to improve calculations of life expectancy and relate them to pathological correlates such as osteoporosis, separate neural arches, spina bifida and arthritis along with regular growth changes. This capability enables much better utilization of pre-contact skeletons and therefore of the numbers, density and composition of populations before European contact. The general picture emerging from skeletal studies, census records and living populations is, in Arctic Eskimos, one of high fertility, high mortality and short length of life, with a slow population growth rate. Aleuts show lower fertility, lower mortality and longer length of life, also with a low population growth rate. 相似文献
992.
Therese Garrick Nina Sundqvist Timothy Dobbins Liza Azizi Clive Harper 《Cell and tissue banking》2009,10(4):309-315
Whilst mainstream transplant literature provides valuable insights into the influences on families to donate organs and tissues
for transplant, the relevance of these findings in relation to organ donation for research remain speculative. The present
study aims to expand the research donation literature, by exploring factors that influence a family’s decision to donate brain
tissue to neuroscience research. The verbal responses of the senior available next-of-kin (NOK), to the question of brain
donation for research, are analysed. The donation rate was high (54%) over the 5-year-period. NOK relationship to the deceased,
and post mortem interval were the main factors associated with a positive donation. Parents were most likely to donate and
this may result from a lifetime of decision-making on behalf of the deceased. Also, the longer the interval between death
of the potential donor and the question being asked, the greater the likelihood of donation. 相似文献
993.
Monemdjou S Hofmann WE Kozak LP Harper ME 《American journal of physiology. Endocrinology and metabolism》2000,279(4):E941-E946
Mice having targeted inactivation of uncoupling protein 1 (UCP1) are cold sensitive but not obese (Enerb?ck S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper M-E, and Kozak LP. Nature 387: 90-94, 1997). Recently, we have shown that proton leak in brown adipose tissue (BAT) mitochondria from UCP1-deficient mice is insensitive to guanosine diphosphate (GDP), a well known inhibitor of UCP1 activity (Monemdjou S, Kozak LP, and Harper M-E. Am J Physiol Endocrinol Metab 276: E1073-E1082, 1999). Moreover, despite a fivefold increase of UCP2 mRNA in BAT of UCP1-deficient mice, we found no differences in the overall kinetics of this GDP-insensitive proton leak between UCP1-deficient mice and controls. Based on these findings, which show no adaptive increase in UCP1-independent leak in BAT, we hypothesized that adaptive thermogenesis may be occurring in other tissues of the UCP1-deficient mouse (e.g., skeletal muscle), thus allowing them to maintain their normal resting metabolic rate, feed efficiency, and adiposity. Here, we report on the overall kinetics of the mitochondrial proton leak, respiratory chain, and ATP turnover in skeletal muscle mitochondria from UCP1-deficient and heterozygous control mice. Over a range of mitochondrial protonmotive force (Deltap) values, leak-dependent oxygen consumption is higher in UCP1-deficient mice compared with controls. State 4 (maximal leak-dependent) respiration rates are also significantly higher in the mitochondria of mice deficient in UCP1, whereas state 4 Deltap is significantly lower. No significant differences in state 3 respiration rates or Deltap values were detected between the two groups. Thus the altered kinetics of the mitochondrial proton leak in skeletal muscle of UCP1-deficient mice indicate a thermogenic mechanism favoring the lean phenotype of the UCP1-deficient mouse. 相似文献
994.
A major cue to the location of a sound source is the interaural time difference (ITD)–the difference in sound arrival time at the two ears. The neural representation of this auditory cue is unresolved. The classic model of ITD coding, dominant for a half-century, posits that the distribution of best ITDs (the ITD evoking a neuron’s maximal response) is unimodal and largely within the range of ITDs permitted by head-size. This is often interpreted as a place code for source location. An alternative model, based on neurophysiology in small mammals, posits a bimodal distribution of best ITDs with exquisite sensitivity to ITDs generated by means of relative firing rates between the distributions. Recently, an optimal-coding model was proposed, unifying the disparate features of these two models under the framework of efficient coding by neural populations. The optimal-coding model predicts that distributions of best ITDs depend on head size and sound frequency: for high frequencies and large heads it resembles the classic model, for low frequencies and small head sizes it resembles the bimodal model. The optimal-coding model makes key, yet unobserved, predictions: for many species, including humans, both forms of neural representation are employed, depending on sound frequency. Furthermore, novel representations are predicted for intermediate frequencies. Here, we examine these predictions in neurophysiological data from five mammalian species: macaque, guinea pig, cat, gerbil and kangaroo rat. We present the first evidence supporting these untested predictions, and demonstrate that different representations appear to be employed at different sound frequencies in the same species. 相似文献
995.
Biochemical analysis of the Kruppel-associated box (KRAB) transcriptional repression domain 总被引:10,自引:0,他引:10
Peng H Begg GE Harper SL Friedman JR Speicher DW Rauscher FJ 《The Journal of biological chemistry》2000,275(24):18000-18010
996.
Wang CJ Nan GL Kelliher T Timofejeva L Vernoud V Golubovskaya IN Harper L Egger R Walbot V Cande WZ 《Development (Cambridge, England)》2012,139(14):2594-2603
997.
Bart H. Harper Liping Wang Cheng Zhu Nam F. Kar Bing Li Christopher R. Moyes Stephen D. Goble Melissa Costa Karen Dingley Jerry Di Salvo Sookhee N. Ha Amanda Hurley Xiaofang Li Randy R. Miller Hiroshi Nagabukuro Gino M. Salituro Sean Smith Mary Struthers Richard Berger 《Bioorganic & medicinal chemistry letters》2017,27(4):1094-1098
The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human β3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established β3 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed. 相似文献
998.
Absence of nucleosomes in a histone-containing nucleoprotein complex obtained by dissociation of purified SV40 virions 总被引:10,自引:0,他引:10
Reduction of disulfide bonds involving the major capsid protein with dithiothreitol and removal of the calcium ions by EGTA disrupts the simian virus 40 virions. This process yields normal circular viral minichromosomes containing the four core histones and traces of the capsid proteins at pH values higher than 8.5. However, when carried out at pH 7.5, this procedure yields nucleoprotein complexes that contain both histones and the viral structural proteins. These pH 7.5 complexes appear as circular structures with a mean of 93 +/- 17 beads with a diameter of 7 nm and no visible nucleosomes when observed by electron microscopy. In contrast to the compaction of the viral DNA in minichromosomes, the length of these beaded structures is roughly the same as free DNA. We suggest that VP1, the major capsid protein, can act as a nucleosome unfolding agent in neutral pH and low ionic strength. 相似文献
999.
David O. Bates Athina Mavrou Yan Qiu James G. Carter Maryam Hamdollah-Zadeh Shaney Barratt Melissa V. Gammons Ann B. Millar Andrew H. J. Salmon Sebastian Oltean Steven J. Harper 《PloS one》2013,8(7)
Vascular Endothelial Growth Factor-A (VEGF-A) can be generated as multiple isoforms by alternative splicing. Two families of isoforms have been described in humans, pro-angiogenic isoforms typified by VEGF-A165a, and anti-angiogenic isoforms typified by VEGF-A165b. The practical determination of expression levels of alternative isoforms of the same gene may be complicated by experimental protocols that favour one isoform over another, and the use of specific positive and negative controls is essential for the interpretation of findings on expression of the isoforms. Here we address some of the difficulties in experimental design when investigating alternative splicing of VEGF isoforms, and discuss the use of appropriate control paradigms. We demonstrate why use of specific control experiments can prevent assumptions that VEGF-A165b is not present, when in fact it is. We reiterate, and confirm previously published experimental design protocols that demonstrate the importance of using positive controls. These include using known target sequences to show that the experimental conditions are suitable for PCR amplification of VEGF-A165b mRNA for both q-PCR and RT-PCR and to ensure that mispriming does not occur. We also provide evidence that demonstrates that detection of VEGF-A165b protein in mice needs to be tightly controlled to prevent detection of mouse IgG by a secondary antibody. We also show that human VEGF165b protein can be immunoprecipitated from cultured human cells and that immunoprecipitating VEGF-A results in protein that is detected by VEGF-A165b antibody. These findings support the conclusion that more information on the biology of VEGF-A165b isoforms is required, and confirm the importance of the experimental design in such investigations, including the use of specific positive and negative controls. 相似文献
1000.
New Species of Spirotrichonympha from Reticulitermes and the Relationships Among Genera in Spirotrichonymphea (Parabasalia) 下载免费PDF全文
Gillian H. Gile Erick R. James Vera Tai James T. Harper Trevor L. Merrell Vittorio Boscaro Filip Husník Rudolf H. Scheffrahn Patrick J. Keeling 《The Journal of eukaryotic microbiology》2018,65(2):159-169
Spirotrichonymphea is a class of hypermastigote parabasalids defined by their spiral rows of many flagella. They are obligate hindgut symbionts of lower termites. Despite more than 100 yr of morphological and ultrastructural study, the group remains poorly characterised by molecular data and the phylogenetic positions and taxonomic validity of most genera remain in question. The genus Spirotrichonympha has been reported to inhabit several termite genera, including Reticulitermes, Coptotermes, and Hodotermopsis. The type species for this genus, Spirotrichonympha flagellata, was described from Reticulitermes lucifugus but no molecular data are yet available for this species. In this study, three new Spirotrichonympha species are described from three species of Reticulitermes. Their molecular phylogenetic position indicates that the genus is not monophyletic, as Spirotrichonympha species from Coptotermes, Paraneotermes, and Hodotermopsis branch separately. In contrast, the genus Holomastigotoides is monophyletic, as demonstrated using new sequences from Holomastigotoides species. The presence of Holomastigotoides in Prorhinotermes and the distinct phylogenetic positions of Spirotrichonympha from Reticulitermes and Coptotermes are consistent with a previously proposed symbiont fauna replacement in the ancestor of Reticulitermes. 相似文献