全文获取类型
收费全文 | 186篇 |
免费 | 8篇 |
出版年
2022年 | 4篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 7篇 |
2014年 | 6篇 |
2013年 | 14篇 |
2012年 | 6篇 |
2011年 | 13篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 10篇 |
2007年 | 17篇 |
2006年 | 4篇 |
2005年 | 8篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 5篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 19篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有194条查询结果,搜索用时 15 毫秒
1.
D Gloag 《BMJ (Clinical research ed.)》1982,284(6328):1509-1510
2.
James M. Chen Rosalyn Grad Regina Monaco Matthew R. Pincus 《Journal of Protein Chemistry》1996,15(1):11-16
rap-1A, an anti-oncogene-encoded protein, is aras-p21-like protein whose sequence is over 80% homologous to p21 and which interacts with the same intracellular target proteins and is activated by the same mechanisms as p21, e.g., by binding GTP in place of GDP. Both interact with effector proteins in the same region, involving residues 32–47. However, activated rap-1A blocks the mitogenic signal transducing effects of p21. Optimal sequence alignment of p21 and rap-1A shows two insertions of rap-1A atras positions 120 and 138. We have constructed the three-dimensional structure of rap-1A bound to GTP by using the energy-minimized three-dimensional structure ofras-p21 as the basis for the modeling using a stepwise procedure in which identical and homologous amino acid residues in rap-1A are assumed to adopt the same conformation as the corresponding residues in p21. Side-chain conformations for homologous and nonhomologous residues are generated in conformations that are as close as possible to those of the corresponding side chains in p21. The entire structure has been subjected to a nested series of energy minimizations. The final predicted structure has an overall backbone deviation of 0.7 å from that ofras-p21. The effector binding domains from residues 32–47 are identical in both proteins (except for different side chains of different residues at position 45). A major difference occurs in the insertion region at residue 120. This region is in the middle of another effector loop of the p21 protein involving residues 115–126. Differences in sequence and structure in this region may contribute to the differences in cellular functions of these two proteins. 相似文献
3.
4.
Rosalyn M. Price-Waldman Allison J. Shultz Kevin J. Burns 《Evolution; international journal of organic evolution》2020,74(6):1155-1169
Although evolutionary theory predicts an association between the evolution of elaborate ornamentation and speciation, empirical evidence for links between speciation and ornament evolution has been mixed. In birds, the evolution of increasingly complex and colorful plumage may promote speciation by introducing prezygotic mating barriers. However, overall changes in color complexity, including both increases and decreases, may also promote speciation by altering the sexual signals that mediate reproductive choices. Here, we examine the relationship between complex plumage and speciation rates in the largest family of songbirds, the tanagers (Thraupidae). First, we test whether species with more complex plumage coloration are associated with higher speciation rates and find no correlation. We then test whether rates of male or female plumage color complexity evolution are correlated with speciation rates. We find that elevated rates of plumage complexity evolution are associated with higher speciation rates, regardless of sex and whether species are evolving more complex or less complex ornamentation. These results extend to whole-plumage color complexity and regions important in signaling (crown and throat) but not nonsignaling regions (back and wingtip). Our results suggest that the extent of change in plumage traits, rather than overall values of plumage complexity, may play a role in speciation. 相似文献
5.
Previously, we demonstrated an autoregulatory feedback loop in the rat carotid body (CB), involving presynaptic GABA(B) receptor-mediated activation of the background K(+) channel TASK-1. Here, we examined the effects of the selective GABA(B) receptor agonist baclofen on K(+) currents in immortalised adrenomedullary chromaffin (MAH) cells, which share the same sympathoadrenal lineage as CB type I cells. Under symmetrical K(+) conditions, 50 microM baclofen enhanced a K(+) current which was linear and reversed close to 0 mV. Under physiological K(+) conditions, baclofen enhanced outward K(+) current and caused membrane hyperpolarisation, effects inhibited by 100 nM CGP 55845. Current enhancement was virtually abolished in the presence of 300 microM Zn(2+), a selective inhibitor of TASK-1. When recording membrane potential from MAH cells in clusters, hypoxic depolarisation was augmented by 100 nM CGP 55845. These data demonstrate that GABA(B) receptors mediate autoreceptor feedback in the adrenal medulla presumably via TASK-1, demonstrating a common autoregulatory feedback pathway in neurosecretory, chemosensitive cells. 相似文献
6.
The different physiological roles of interleukin-1alpha (IL-1alpha) and interleukin-1beta (IL-1beta) are not well understood, especially when considering the apparent overlap and redundancy of the two IL-1 molecules. Characterization of IL-1alpha and IL-1beta expression was performed in this study in organs from young and old mice, using immunohistochemistry and ELISA (enzyme-linked immunosorbent assay). The results indicate that organ IL-1alpha and IL-1beta display different patterns of expression: IL-1alpha is manifested more prominently in lymphoreticular organs (lungs, small intestine, spleen, liver), while IL-1beta is more evident in highly specialized and more vulnerable organs, which do not play a leading role in defense against infections and intoxication (heart, brain, skeletal muscle, kidney). This differential expression is more accentuated in old mice, possibly pointing to the special relevance of these cytokines to organ homeostasis in old age. These findings may shed new light on the physiological functions of IL-1alpha and IL-1beta, and may also lead to the development of improved therapeutic approaches, based on the specific manipulation of these cytokines. 相似文献
7.
The clinicopathological and gene expression patterns associated with ulceration of primary melanoma
下载免费PDF全文
![点击此处可从《Pigment cell & melanoma research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rosalyn Jewell Faye Elliott Jonathan Laye Jérémie Nsengimana John Davies Christy Walker Caroline Conway Angana Mitra Mark Harland Martin G. Cook Andy Boon Sarah Storr Sabreena Safuan Stewart G. Martin Karin Jirström Håkan Olsson Christian Ingvar Martin Lauss Tim Bishop Göran Jönsson Julia Newton‐Bishop 《Pigment cell & melanoma research》2015,28(1):94-104
Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502‐gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density. Gene expression results were validated using a whole genome array in two independent sample sets. Ulceration of primary melanomas was associated with more proliferative tumors, tumor vessel invasion, and increased microvessel density. Infiltration of tumors with greater number of macrophages and gene expression pathways associated with wound healing and up‐regulation of pro‐inflammatory cytokines suggests that ulceration is associated with tumor‐related inflammation. The relative benefit from interferon reported in patients with ulcerated tumors may reflect modification of signaling pathways involved in inflammation. 相似文献
8.
Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier 总被引:1,自引:0,他引:1
Mellersh CS Graves KT McLaughlin B Ennis RB Pettitt L Vaudin M Barnett KC 《The Journal of heredity》2007,98(5):531-533
Primary hereditary cataract (HC) is one of the most common disorders in purebred dogs and is a leading cause of blindness. Boston Terriers suffer from 2 distinct forms of HC which occur at different ages and which are different in their appearance and progression. Early-onset hereditary cataract (EHC) affects dogs within the first few months of life, is always progressive and bilateral, and results in total blindness, whereas late-onset hereditary cataract (LHC) in general affects dogs over the age of 3 and is more variable in its clinical phenotype, age of onset, progression, and the degree to which vision is impaired. A mutation in HSF4 has recently been reported in a small number of Boston Terriers affected with EHC. In this study, we analyzed 22 additional Boston Terriers affected with early-onset cataract to confirm that the HSF4 mutation is causative for this form of cataract in this breed. In addition, we analyzed 40 Boston Terriers that were either clinically clear or affected with LHC for the presence or absence of the HSF4 mutation. By also sequencing HSF4 in dogs affected with LHC, we conclude that HSF4 is not associated with the development of the late-onset form of cataract and that the 2 forms of cataract in this breed are therefore genetically discrete conditions. 相似文献
9.
Johns P Pereira SL Leonard AE Mukerji P Shalwitz RA Dowlati L Phillips RR Bergana MS Holton JD Das T 《Current microbiology》2007,54(2):131-135
Adenosine 5′-diphosphoribose (ADP-ribose) has been identified as a significant contributor to the anti-cytotoxic activity
of Lactobacillus bulgaricus extracts. Although the biological activities associated with the administration of probiotic bacteria and components thereof
are sometimes attributed to the peptidoglycans that comprise a substantial portion of the Gram-positive bacterial cell wall,
we found that the beta-nicotine adenine dinucleotide (NAD) hydrolysis product ADP-ribose was a significant contributor to
the observed anti-cytotoxicity in our L. bulgaricus extracts. The ADP-ribose was isolated, identified, and quantitated by high performance liquid chromatography (HPLC) and by
nuclear magnetic resonance (NMR) spectroscopy. ADP-ribose levels as low as 5 mg/L exhibited a measurable inhibition of tumor
necrosis factor alpha (TNF-α) mediated cytotoxicity in an in vitro cell assay, whereas the ADP-ribose content of the L. bulgaricus extracts often exceeded 5 mg/g dry weight. 相似文献