全文获取类型
收费全文 | 344篇 |
免费 | 37篇 |
专业分类
381篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2016年 | 4篇 |
2015年 | 12篇 |
2014年 | 15篇 |
2013年 | 22篇 |
2012年 | 18篇 |
2011年 | 20篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 10篇 |
2005年 | 15篇 |
2004年 | 7篇 |
2003年 | 13篇 |
2002年 | 14篇 |
2001年 | 17篇 |
2000年 | 13篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1968年 | 2篇 |
1928年 | 2篇 |
1927年 | 3篇 |
1923年 | 3篇 |
1909年 | 1篇 |
1902年 | 2篇 |
1897年 | 1篇 |
排序方式: 共有381条查询结果,搜索用时 10 毫秒
121.
Molecular evidence for the rapid propagation of mouse t haplotypes from a single, recent, ancestral chromosome 总被引:11,自引:0,他引:11
Silver LM; Hammer M; Fox H; Garrels J; Bucan M; Herrmann B; Frischauf AM; Lehrach H; Winking H; Figueroa F 《Molecular biology and evolution》1987,4(5):473-482
Mouse t haplotypes are variant forms of chromosome 17 that exist at high
frequencies in worldwide populations of two species of commensal mice. To
determine both the relationship of t haplotypes to each other and the
species within which they exist, 35 representative t haplotypes were
analyzed by means of 10 independent molecular probes, including five DNA
clones and five polypeptide spots identified by means of two- dimensional
gel electrophoresis. All of the tested haplotypes were found to share
restriction fragments and polypeptide spots that are absent in mice
carrying wild-type forms of chromosome 17. This observation provides the
first direct evidence that all of the known t haplotypes are descendents of
a single ancestral chromosome. The absence of variation among t haplotypes
could mean that this ancestral chromosome existed relatively recently, in
which case it would be necessary to postulate introgressions of t
haplotypes across species lines to explain their presence in both Mus
domesticus and M. musculus. Alternatively, it is possible that the
ancestral chromosome existed prior to the split between M. domesticus and
M. musculus and that, by chance, our probes fail to detect polymorphisms
that exist among the t haplotypes. A further result of our analysis is the
characterization of a partial t haplotype in a wild population of Israeli
mice.
相似文献
122.
Ricciardelli C Russell DL Ween MP Mayne K Suwiwat S Byers S Marshall VR Tilley WD Horsfall DJ 《The Journal of biological chemistry》2007,282(14):10814-10825
Previous studies have demonstrated that high levels of hyaluronan (HA) and the chondroitin sulfate proteoglycan, versican in the peritumoral stroma are associated with metastatic spread of clinical prostate cancer. In vitro integration of HA and versican into a pericellular sheath is a prerequisite for proliferation and migration of vascular smooth muscle cells. In this study, a particle exclusion assay was used to determine whether human prostate cancer cell lines are capable of assembling a pericellular sheath following treatment with versican-containing medium and whether formation of a pericellular sheath modulated cell motility. PC3 and DU145, but not LNCaP cells formed prominent polarized pericellular sheaths following treatment with prostate fibroblast-conditioned medium. The capacity to assemble a pericellular sheath correlated with the ability to express membranous HA receptor, CD44. HA and versican histochemical staining were observed surrounding PC3 and DU145 cells following treatment with prostatic fibroblast-conditioned medium. The dependence on HA for integrity of the pericellular sheath was demonstrated by its removal following treatment with hyaluronidase. Purified versican or conditioned medium from Chinese hamster ovary K1 cells overexpressing versican V1, but not conditioned medium from parental cells, promoted pericellular sheath formation and motility of PC3 cells. Using time lapse microscopy, motile PC3 cells treated with versican but not non-motile cells exhibited a polar pericellular sheath. Polar pericellular sheath was particularly evident at the trailing edge but was excluded from the leading edge of PC3 cells. These studies indicate that prostate cancer cells recruit stromal components to remodel their pericellular environment and promote their motility. 相似文献
123.
A parsimony analysis was performed on restriction sites at the Hba-ps4
pseudogene locus within one of four inversions associated with mouse t
haplotypes. The results suggest that all t haplotypes form a monophyletic
group and that the in (17)4 inversion originated before the radiation of
the Mus musculus species complex but after the divergence of the lineages
leading to M. spretus, M. abbotti, and M. hortulanus. A time frame based on
the evolutionary rate of mouse pseudogenes places the origin of this t
haplotype inversion at 1.5 Mya, or approximately 1.5 Myr after the origin
of the more proximal t complex inversion, in (17)2. The accumulated
evidence indicates that complete t haplotypes have been assembled in a
stepwise manner, with each of these inversions occurring on separate
chromosomal lineages and at different evolutionary times. In addition, the
evolutionary relationships of pseudogene sequences resulting from genetic
exchange between wild-type and t haplotype alleles were examined. Analysis
of sequences from the 5' and 3' sides of a putative site of recombination
resulted in cladograms with different topologies. The implications for
hypotheses concerning the evolutionary forces acting on t haplotypes and
their rapid propagation throughout worldwide populations of mice are
discussed.
相似文献
124.
Decreased Levels of BAG3 in a Family With a Rare Variant and in Idiopathic Dilated Cardiomyopathy 下载免费PDF全文
Arthur M. Feldman Rene L. Begay Tijana Knezevic Valerie D. Myers Dobromir B. Slavov Weizhong Zhu Katherine Gowan Sharon L. Graw Kenneth L. Jones Douglas G. Tilley Ryan C. Coleman Paul Walinsky Joseph Y. Cheung Luisa Mestroni Kamel Khalili Mathew R.G. Taylor 《Journal of cellular physiology》2014,229(11):1697-1702
The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole‐exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10‐nucleotide deletion in the BCL2‐associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C‐terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end‐stage HF undergoing cardiac transplantation when compared with non‐failing controls. Diminished levels of BAG3 protein may be associated with both familial and non‐familial forms of dilated cardiomyopathy. J. Cell. Physiol. 229: 1697–1702, 2014. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 相似文献
125.
126.
False-positive TUNEL staining observed in SV40 based transgenic murine prostate cancer models 总被引:1,自引:0,他引:1
M. D. Lawrence B. J. Blyth R. J. Ormsby W. D. Tilley P. J. Sykes 《Transgenic research》2013,22(5):1037-1047
The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) and LADY (Probasin-large T antigen transgenic mouse) mice are widely used autochthonous models of prostate cancer. Both models utilise probasin promoters to direct androgen-regulated expression of oncogenic SV40 specifically to epithelial cells of the mouse prostate. The oncogenic processes and phenotypes which result mimic many features of human prostate cancer, making these transgenic mouse models useful experimental systems. The terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP in situ nick end labelling (TUNEL) assay is a commonly used method for the detection of cells undergoing apoptosis. In this study, we demonstrate false-positive TUNEL staining in frozen prostate tissue from TRAMP and LADY mice, which was not observed in non-transgenic control animals and is not due to non-specific binding of labelled-dUTP substrate. The false-positive signal co-localised with large SV40 T-antigen expression. False-positive signal was apparent using multiple commercial TUNEL kits with different detection systems. These results caution against the use of the TUNEL assay for detection of apoptosis in frozen prostate tissue of large T-antigen based autochthonous transgenic models of prostate cancer. 相似文献
127.
Laboratory bioassays were conducted to determine the effects of two carbamates, carbofuran (an acetylcholinesterase inhibitor) and fenoxycarb (a juvenile hormone analog), on survival and infectivity of the infective juveniles (IJ) of Steinernema feltiae Umeå strain and Steinernema carpocapsae All strain. Both insecticides caused mortality of IJ in a dose-related fashion. The two nematode species were equally sensitive to fenoxycarb (LD₅₀ ca. 0.03mg/ml). Whereas IJ of S. feltiae were several orders of magnitude more sensitive to carbofuran (LD₅₀ ≤ 0.2 μg/ml) than to fenoxycarb, S. carpocapsae IJ displayed approximately the same degree of sensitivity to carbofuran (LD₅₀ 0.01-0.03 mg/ml) as they did toward fenoxycarb. Toxicity of the carbamates was the same at all exposure periods from 24 to 168 hours'' duration. Determinations of infective doses of nematodes required to cause 50% mortality of Galleria mellonella larvae showed that the infectivity of IJ that survived exposure to either of the two carbamates was not compromised by treatment. 相似文献
128.
Paul J. McMillan Mauro Maiorca Eric Hanssen Shannon Kenny Rebecca A. Muhle Martin Melcher David A. Fidock Joseph D. Smith Matthew W. A. Dixon Leann Tilley 《Cellular microbiology》2013,15(8):1401-1418
The human malaria parasite, Plasmodium falciparum, modifies the red blood cells (RBCs) that it infects by exporting proteins to the host cell. One key virulence protein, P. falciparum Erythrocyte Membrane Protein‐1 (PfEMP1), is trafficked to the surface of the infected RBC, where it mediates adhesion to the vascular endothelium. We have investigated the organization and development of the exomembrane system that is used for PfEMP1 trafficking. Maurer's cleft cisternae are formed early after invasion and proteins are delivered to these (initially mobile) structures in a temporally staggered and spatially segregated manner. Membrane‐Associated Histidine‐Rich Protein‐2(MAHRP2)‐containing tether‐like structures are generated as early as 4 h post invasion and become attached to Maurer's clefts. The tether/Maurer's cleft complex docks onto the RBC membrane at ~ 20 h post invasion via a process that is not affected by cytochalasin D treatment. We have examined the trafficking of a GFP chimera of PfEMP1 expressed in transfected parasites. PfEMP1B‐GFP accumulates near the parasite surface, within membranous structures exhibiting a defined ultrastructure, before being transferred to pre‐formed mobile Maurer's clefts. Endogenous PfEMP1 and PfEMP1B‐GFP are associated with Electron‐Dense Vesicles that may be responsible for trafficking PfEMP1 from the Maurer's clefts to the RBC membrane. 相似文献
129.
Tilley JW Kaplan G Rowan K Schwinge V Wolitzky B 《Bioorganic & medicinal chemistry letters》2001,11(1):1-4
A series of imides and lactams derived from 4-amino-N-benzylpyroglutamyl-L-phenylalanine was prepared and evaluated for activity as VCAM/VLA-4 antagonists. Imides were more potent than the corresponding lactams; several had subnanomolar IC50s in an ELISA based assay and were also highly effective at blocking VLA-4 expressing Ramos cell binding to VCAM coated plates. 相似文献
130.
Dixon MW Kenny S McMillan PJ Hanssen E Trenholme KR Gardiner DL Tilley L 《Molecular microbiology》2011,81(4):982-993
The malaria parasite Plasmodium falciparum assembles knob structures underneath the erythrocyte membrane that help present the major virulence protein, P. falciparum erythrocyte membrane protein-1 (PfEMP1). Membranous structures called Maurer's clefts are established in the erythrocyte cytoplasm and function as sorting compartments for proteins en route to the RBC membrane, including the knob-associated histidine-rich protein (KAHRP), and PfEMP1. We have generated mutants in which the Maurer's cleft protein, the ring exported protein-1 (REX1) is truncated or deleted. Removal of the C-terminal domain of REX1 compromises Maurer's cleft architecture and PfEMP1-mediated cytoadherance but permits some trafficking of PfEMP1 to the erythrocyte surface. Deletion of the coiled-coil region of REX1 ablates PfEMP1 surface display, trapping PfEMP1 at the Maurer's clefts. Complementation of mutants with REX1 partly restores PfEMP1-mediated binding to the endothelial cell ligand, CD36. Deletion of the coiled-coil region or complete deletion of REX1 is tightly associated with the loss of a subtelomeric region of chromosome 2, encoding KAHRP and other proteins. A KAHRP-green fluorescent protein (GFP) fusion expressed in the REX1-deletion parasites shows defective trafficking. Thus, loss of functional REX1 directly or indirectly ablates the assembly of the P. falciparum virulence complex at the surface of host erythrocytes. 相似文献