全文获取类型
收费全文 | 642篇 |
免费 | 70篇 |
出版年
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 20篇 |
2014年 | 24篇 |
2013年 | 32篇 |
2012年 | 29篇 |
2011年 | 35篇 |
2010年 | 25篇 |
2009年 | 24篇 |
2008年 | 25篇 |
2007年 | 32篇 |
2006年 | 29篇 |
2005年 | 16篇 |
2004年 | 28篇 |
2003年 | 26篇 |
2002年 | 18篇 |
2001年 | 14篇 |
2000年 | 23篇 |
1999年 | 22篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 9篇 |
1984年 | 19篇 |
1983年 | 9篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 8篇 |
1978年 | 10篇 |
1976年 | 9篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1968年 | 3篇 |
1934年 | 3篇 |
1931年 | 3篇 |
排序方式: 共有712条查询结果,搜索用时 15 毫秒
81.
Dietary restriction (DR) extends life span in diverse organisms, including mammals, and common mechanisms may be at work. DR is often known as calorie restriction, because it has been suggested that reduction of calories, rather than of particular nutrients in the diet, mediates extension of life span in rodents. We here demonstrate that extension of life span by DR in Drosophila is not attributable to the reduction in calorie intake. Reduction of either dietary yeast or sugar can reduce mortality and extend life span, but by an amount that is unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than does sugar. Calorie intake is therefore not the key factor in the reduction of mortality rate by DR in this species. 相似文献
82.
Suzanne V Frankfort Valerie D Doodeman Remco Bakker Linda R Tulner Jos PCM van Campen Paul HM Smits Jos H Beijnen 《Molecular neurodegeneration》2006,1(1):1-5
Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects. 相似文献
83.
Bollen AM Baskin CR Treuting PM 《Comparative medicine》2006,56(4):245; author reply 245-245; author reply 246
84.
85.
Bowers K Piper SC Edeling MA Gray SR Owen DJ Lehner PJ Luzio JP 《The Journal of biological chemistry》2006,281(8):5094-5105
Models for protein sorting at multivesicular bodies in the endocytic pathway of mammalian cells have relied largely on data obtained from yeast. These data suggest the essential role of four ESCRT complexes in multivesicular body protein sorting. However, the putative mammalian ESCRTII complex (hVps25p, hVps22p, and hVps36p) has no proven functional role in endosomal transport. We have characterized the human ESCRTII complex and investigated its function in endosomal trafficking. The human ESCRTII proteins interact with one another, with hVps20p (a component of ESCRTIII), and with their yeast homologues. Our interaction data from yeast two-hybrid studies along with experiments with purified proteins suggest an essential role for the N-terminal domain of hVps22p in the formation of a heterotetrameric ESCRTII complex. Although human ESCRTII is found in the cytoplasm and in the nucleus, it can be recruited to endosomes upon overexpression of dominant-negative hVps4Bp. Interestingly, we find that small interference RNA depletion of mammalian ESCRTII does not affect degradation of epidermal growth factor, a known cargo of the multivesicular body protein sorting pathway. We also show that depletion of the deubiquitinating enzymes AMSH (associated molecule with the SH3 domain of STAM (signal transducing adaptor molecule)) and UBPY (ubiquitin isopeptidase Y) have opposite effects on epidermal growth factor degradation, with UBPY depletion causing dramatic swelling of endosomes. Down-regulation of another cargo, the major histocompatibility complex class I in cells expressing the Kaposi sarcoma-associated herpesvirus protein K3, is unaffected in ESCRTII-depleted cells. Our data suggest that mammalian ESCRTII may be redundant, cargo-specific, or not required for protein sorting at the multivesicular body. 相似文献
86.
There is limited research on relationships between root characteristics and soil chemical properties and processes. Because
previous studies have shown specific C compounds may release previously sorbed P and make P more plant-available, crops which
contribute to high soil C levels could play an important role in soil P cycling. The objectives of this study were to determine
(1) whether rotation crops had different amounts of root growth, (2) whether different amounts of root growth among the crop
species could be related to different levels of soluble soil C and (3) whether there were differences in P concentration among
the soils under different crops that could be related to soluble C soil concentration. Roots and soil from potato (Solanum tuberosum L.), barley (Hordeum vulgare L.), soybean (Glycine max (L.) Merr.), and a forage consisting of alfalfa (Medicago sativa L.) and timothy (Phleum pretense L.) were sampled from the Aroostook Research Farm in Presque Isle, Maine, during the summers of 2003 and 2004 to determine
root length density (RLD) and soluble C and P concentrations. Half of the sampled plots were amended with beef manure and
half were not amended. Barley and forage consistently had higher RLD than potato or soybean crops. Barley and forage typically
had higher concentrations of soluble soil C than potato or soybean, but the differences were significant at only three of
the five sampling dates. RLD was significantly correlated to soluble C (r=0.56) only for amended soils on the August 2003 sampling date. For other dates r values were non-significant and ranged from 0.32 to 0.49. As with soil C, soluble soil P levels were typically higher in
barley and forage than in potato or soybean crops. Significant differences were detected at four of the five sampling dates.
Correlations between soluble C and soluble P were significant at two of the five sampling dates (r = 0.58 and 0.62) in amended soils and one of five sampling dates (r = 0.80) in unamended soils. Although the correlations between RLD and soluble C were not significant at every sampling date,
the August 2003 data do suggest a possible effect of roots on soluble C. In addition, significant correlations between soluble
C and soluble P at several sampling dates suggest a relationship between these parameters. Therefore cropping systems that
include crops with higher amounts of root growth may promote increased soluble soil C levels and enhance P bioavailability. 相似文献
87.
Lissauer D Piper K Goodyear O Kilby MD Moss PA 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(2):1072-1080
Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-specific T cells in women who were pregnant with a male fetus. Fetal-specific CD8(+) T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy and that unlike reports from some murine models, fetal-specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-related complications. 相似文献
88.
Sakata I Park WM Walker AK Piper PK Chuang JC Osborne-Lawrence S Zigman JM 《American journal of physiology. Endocrinology and metabolism》2012,302(10):E1300-E1310
The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with d-glucose concentration. Insulin blocked ghrelin release, but only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory effect of high d-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATP-sensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain. 相似文献
89.
X Jiao DJ Kopecky B Fisher DE Piper M Labelle S McKendry M Harrison S Jones J Jaen AK Shiau P Escaron J Danao A Chai P Coward F Kayser 《Bioorganic & medicinal chemistry letters》2012,22(18):5966-5970
The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents. 相似文献
90.