首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3576篇
  免费   232篇
  2023年   21篇
  2022年   33篇
  2021年   76篇
  2020年   53篇
  2019年   56篇
  2018年   92篇
  2017年   75篇
  2016年   136篇
  2015年   188篇
  2014年   199篇
  2013年   258篇
  2012年   294篇
  2011年   293篇
  2010年   176篇
  2009年   177篇
  2008年   214篇
  2007年   204篇
  2006年   174篇
  2005年   184篇
  2004年   163篇
  2003年   154篇
  2002年   146篇
  2001年   28篇
  2000年   31篇
  1999年   38篇
  1998年   25篇
  1997年   35篇
  1996年   33篇
  1995年   24篇
  1994年   30篇
  1993年   25篇
  1992年   15篇
  1991年   15篇
  1990年   10篇
  1989年   8篇
  1988年   10篇
  1987年   10篇
  1986年   7篇
  1985年   9篇
  1984年   10篇
  1983年   5篇
  1982年   7篇
  1980年   9篇
  1979年   4篇
  1978年   4篇
  1977年   4篇
  1976年   5篇
  1973年   7篇
  1971年   4篇
  1946年   5篇
排序方式: 共有3808条查询结果,搜索用时 328 毫秒
141.
142.
143.
We investigated the extent to which exercise-generated heat compensates for regulatory thermogenesis of Eastern house finches (Carpodacus mexicanus Müller) exposed to ambient temperatures (Ta) and convective conditions typical of that which birds experience in nature while perched in the open or foraging on the ground. We addressed the hypothesis that resting and active birds exposed to similar net convective conditions will exhibit similar surface temperatures (Ts) and metabolic energy expenditures. To test this hypothesis, resting birds were exposed to a wind speed equivalent to the treadmill speed (0.5 m s-1) for a hopping bird (active). Ts of resting birds in no wind, resting birds exposed to wind, and active birds were measured with infrared thermography at Ta between 0 degrees and 25 degrees C. Metabolic heat production was estimated from measures of respiratory gases at Ta between -5 degrees and 25 degrees C. For resting birds in no wind, resting birds in wind, and active birds, Ts decreased with decreasing Ta. The effects of variation in Ta on Ts depended on activity level (F=3.91, df=2,40, P=0.0280). The regression relationship of Ts on Ta, however, did not differ significantly between resting birds exposed to wind and active birds (F=0.12, df=2,40, P=0.8865), whereas the slope was lower and intercept higher for resting birds in no wind compared with those of resting birds exposed to wind and active birds combined (F=20.96, df=2,42, P<0.0001). Metabolic heat production for resting birds exposed to wind and active birds increased with decreasing Ta. Average metabolic heat production of resting (46.01 mW g-1+/-10.60 SD) and active birds (47.63 mW g-1+/-8.76 SD) exposed to similar net convective conditions did not differ significantly (F=3.87, df=1,44, P=0.0556). These results support our hypothesis and provide evidence that exercise generated compensates for thermostatic requirements at Ta just below thermoneutrality, which resembles conditions under which house finches naturally forage. We conclude that the compensation of exercise-generated heat for regulatory thermogenesis may occur more frequently under natural environmental conditions than implied by most previous investigators and can result in considerable energy savings for birds living in cold environments.  相似文献   
144.
The effect of pyridoxal 5-phosphate and some other lysine reagents on the purified,reconstituted mitochondrial oxoglutarate transport protein has been investigated. The inhibition ofoxoglutarate/oxoglutarate exchange by pyridoxal 5-phosphate can be reversed by passing theproteoliposomes through a Sephadex column but the reduction of the Schiff's base by sodiumborohydride yielded an irreversible inactivation of the oxoglutarate carrier protein. Pyridoxal5-phosphate, which caused a time- and concentration-dependent inactivation of oxoglutaratetransport with an IC50 of 0.5 mM, competed with the substrate for binding to the oxoglutaratecarrier (K i = 0.4 mM). Kinetic analysis of oxoglutarate transport inhibition by pyridoxal5-phosphate indicated that modification of a single amino acid residue/carrier molecule wassufficient for complete inhibition of oxoglutarate transport. After reduction with sodiumborohydride [3H]pyridoxal 5-phosphate bound covalently to the oxoglutarate carrier. Incubation ofthe proteoliposomes with oxoglutarate or L-malate protected the carrier against inactivationand no radioactivity was found associated with the carrier protein. In contrast, glutarate andsubstrates of other mitochondrial carrier proteins were unable to protect the carrier. Mersalyl,which is a known sulfhydryl reagent, also failed to protect the oxoglutarate carrier againstinhibition by pyridoxal 5-phosphate. These results indicate that pyridoxal 5-phosphateinteracts with the oxoglutarate carrier at a site(s) (i.e., a lysine residue(s) and/or the amino-terminalglycine residue) which is essential for substrate translocation and may be localized at or nearthe substrate-binding site.  相似文献   
145.
Although K-Cl cotransporter (KCC1) mRNA is expressed in manytissues, K-Cl cotransport activity has been measured in few cell types,and detection of endogenous KCC1 polypeptide has not yet been reported.We have cloned the mouse erythroid KCC1 (mKCC1) cDNA and its flankinggenomic regions and mapped the mKCC1 gene to chromosome 8. Threeanti-peptide antibodies raised against recombinant mKCC1 function asimmunoblot and immunoprecipitation reagents. The tissue distributionsof mKCC1 mRNA and protein are widespread, and mKCC1 RNA isconstitutively expressed during erythroid differentiation of ES cells.KCC1 polypeptide or related antigen is present in erythrocytes ofmultiple species in which K-Cl cotransport activity has beendocumented. Erythroid KCC1 polypeptide abundance is elevated inproportion to reticulocyte counts in density-fractionated cells, inbleeding-induced reticulocytosis, in mouse models of sickle celldisease and thalassemia, and in the corresponding human disorders.mKCC1-mediated uptake of 86Rb intoXenopus oocytes requires extracellularCl, is blocked by thediureticR(+)-[2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-indenyl-5-yl-)oxy]acetic acid, and exhibits an erythroid pattern of acute regulation, with activation by hypotonic swelling,N-ethylmaleimide, and staurosporine and inhibition by calyculin and okadaic acid. These reagents and findings will expedite studies of KCC1 structure-function relationships and of the pathobiology of KCC1-mediated K-Cl cotransport.

  相似文献   
146.
We have surveyed 18 natural populations of Drosophila melanogaster for the presence of 23 retrotransposon-gene-association alleles (i.e., the presence of an LTR retrotransposon sequence in or within 1,000 bp of a gene) recently identified in the sequenced D. melanogaster genome. The identified associations were detected only in the D. melanogaster populations. The majority (61%) of the identified retrotransposon-gene associations were present only in the sequenced strain in which they were first identified. Thirty percent of the associations were detected in at least one of the natural populations, and 9% of the associations were detected in all of the D. melanogaster populations surveyed. Sequence analysis of an association allele present in all populations indicates that selection is a significant factor in the spread and/or maintenance of at least some of retroelement-gene associations in D. melanogaster.  相似文献   
147.
Genetic studies have provided remarkable clues to the causes of prostate cancer (PCa). For example, in addition to the expected role of androgens in facilitating the development of PCa, the possibility that infections might lead to prostate cancer has been raised with the identification of RNASEL and MSR1 as familial prostate cancer genes; that insight will profoundly affect future studies and may ultimately lead to new approaches to the prevention of prostate cancer. The identification of key molecular alterations in prostate cancer cells implicates carcinogen defenses, including GSTP1, growth factor signaling pathways (such as NKX3.1, PTEN and p27) and androgens as critical determinants of the phenotype of PCa cells and defines specific targets for detection, diagnosis and treatment of PCa.  相似文献   
148.
The aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18-37 years and fetal gestational age from 37.6-41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel(R) OD-R column and a UV detector. One- or two-compartment models were fitted to data and differences between the (+)-(R) and (-)-(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann-Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher V(d/f) (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and C(l/f) (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t(1/2)beta (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)-(R)-bupivacaine. The combined administration of epinephrine resulted in higher V(d/f) (197.86 vs. 140.60 L for (+)-(R) and 169.46 vs. 132.81 L for (-)-(S)) and t(1/2)beta values (4.36 vs. 3.24 h for (+)-(R) and 4.45 vs. 3.30 h for (-)-(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (-)-(S)-bupivacaine (0.40 vs. 0.35). Chirality 16:65-71, 2004.  相似文献   
149.
The analysis of replication intermediates of a Kluyveromyces lactis chromosomal autonomous replicating sequence (ARS), KARS101, has shown that it is active as a chromosomal replicator. KARS101 contains a 50 bp sequence conserved in two other K. lactis ARS elements. The deletion of the conserved sequence in KARS101 completely abolished replicator activity, in both the plasmids and the chromosome. Gel shift assays indicated that this sequence binds proteins present in K. lactis nuclear extracts, and a 40 bp sequence, previously defined as the core essential for K. lactis ARS function, is required for efficient binding. Reminiscent of the origin replication complex (ORC), the binding appears to be ATP dependent. A similar pattern of protection of the core was seen with in vitro footprinting. KARS101 also functions as an ARS sequence in Saccharomyces cerevisiae. A comparative study using S. cerevisiae nuclear extracts revealed that the sequence required for binding is a dodecanucleotide related to the S. cerevisiae ARS consensus sequence and essential for S. cerevisiae ARS activity.  相似文献   
150.
Aspartyl protease inhibitors (APIs) effectively extend the length and quality of life in human immunodeficiency virus (HIV)-infected patients, but dose-limiting side effects such as lipodystrophy, insulin resistance, and diarrhea have limited their clinical utility. Here, we show that the API nelfinavir induces a secretory form of diarrhea in HIV-infected patients. In vitro studies demonstrate that nelfinavir potentiates muscarinic stimulation of Cl- secretion by T84 human intestinal cell monolayers through amplification and prolongation of an apical membrane Ca2+-dependent Cl- conductance. This stimulated ion secretion is associated with increased magnitude and duration of muscarinically induced intracellular Ca2+ transients via activation of a long-lived, store-operated Ca2+ entry pathway. The enhanced intracellular Ca2+ signal is associated with uncoupling of the Cl- conductance from downregulatory intracellular mediators generated normally by muscarinic activation. These data show that APIs modulate Ca2+ signaling in secretory epithelial cells and identify a novel target for treatment of clinically important API side effects. nelfinavir; clotrimazole; barium  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号