全文获取类型
收费全文 | 339篇 |
免费 | 51篇 |
出版年
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 15篇 |
2015年 | 15篇 |
2014年 | 20篇 |
2013年 | 20篇 |
2012年 | 27篇 |
2011年 | 25篇 |
2010年 | 12篇 |
2009年 | 16篇 |
2008年 | 19篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 15篇 |
2004年 | 12篇 |
2003年 | 13篇 |
2002年 | 18篇 |
2001年 | 13篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1993年 | 2篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1965年 | 4篇 |
1963年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
1957年 | 2篇 |
1952年 | 1篇 |
1943年 | 1篇 |
排序方式: 共有390条查询结果,搜索用时 15 毫秒
1.
Conventional therapies for prostate cancer, especially in its androgen-independent form, may result in the survival of small populations of resistant cells with tumor-initiating potential. These “cancer stem cells” are believed to be responsible for cancer relapse, and therapeutic strategies targeting these cells are of great importance. Telomerase is a ribonucleoprotein enzyme responsible for telomere elongation and is activated in the majority of malignancies, including prostate cancer, but is absent in most normal cells. Putative tumor-initiating cells have significant levels of telomerase, indicating that they are an excellent target for telomerase inhibition therapy. In this review, we present some evidence for the hypothesis that conventional therapies (standard chemotherapy and/or radiation therapy) in combination with telomerase inhibitors may result in effective and more durable responses. 相似文献
2.
In an ultrastructural study of the hepatopancreas of Porcellio scaber, an obligate intracellular parasite, Chlamydia, was noted in the epithelial cells. Although the infection was found to extend the entire length of the hepatopancreas, it was most extensive in the glandular region. Indirect immunofluorescence testing revealed no cross-reactivity with either lymphogranuloma venereum or psittacosis antisera. 相似文献
3.
Roy Ronen Glenn Tesler Ali Akbari Shay Zakov Noah A. Rosenberg Vineet Bafna 《PLoS genetics》2015,11(9)
Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations. 相似文献
4.
Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. 总被引:28,自引:6,他引:22
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
IMR-90 normal human diploid fibroblasts, transfected with a steroid inducible mouse mammary tumor virus-driven simian virus 40 T antigen, were carried through crisis to yield an immortal cell line. Growth was dependent on the presence of the inducer (dexamethasone) during both the extended precrisis life span of the cells and after immortalization. After dexamethasone removal, immortal cells divided once or twice and then accumulated in G1. These results are best explained by a two-stage model for cellular senescence. Mortality stage 1 (M1) causes a loss of mitogen responsiveness and arrest near the G1/S interface and can be bypassed or overcome by the cellular DNA synthesis-stimulating activity of T antigen. Mortality stage 2 (M2) is an independent mechanism that is responsible for the failure of cell division during crisis. The inactivation of M2 is a rare event, probably of mutational origin in human cells, independent of or only indirectly related to the expression of T antigen. Under this hypothesis, T-antigen-immortalized cells contain an active but bypassed M1 mechanism and an inactivated M2 mechanism. These cells are dependent on the continued expression of T antigen for the maintenance of immortality for the same reason that precrisis cells are dependent on T antigen for growth: both contain an active M1 mechanism. 相似文献
5.
Many sperm flagella contain a central pair of singlet tubules surrounded by nine doublet tubules. Insect sperm flagella, however, usually contain in addition to the typical 9+2 arrangement of tubules, an additional row of nine singlet tubules which are called accessory tubules. Each of these accessory tubules in the Colorado potato beetle (Leptinotarsa decemlineata (Say)) contains a single central prototubule surrounded by an array of 15 or 16 peripheral prototubules. The number of prototubules in the accessory tubules of Leptinotarsa decemlineata was determined with an electron microscope and image details were reinforced by the rotation techniques of Markham. 相似文献
6.
Steroid Lysis of Protoplasts and Effects of Stabilizers and Steroid Antagonists 总被引:1,自引:1,他引:0
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Six synthetic antimicrobial steroids were examined for indications of their mechanism of action. Dequadin acetate, cetyl pyridinium chloride (CPC), and sodium deoxycholate were studied for comparison. Aerated cells of Sarcina lutea were washed, suspended in 1.06 M sucrose, and converted to protoplasts with 20 mug/ml of lysozyme. Lysis was measured optically at 650 mmu as a decrease in optical density. Screening tests with 50 mug/ml of each compound showed five steroids and CPC to be lytic. Protoplasts were strongly protected from lysis by pretreatment with 0.001 to 0.004 M spermine tetrahydrochloride. Other polyamines, such as spermidine phosphate, were less protective, and putrescine was ineffective. Uranyl nitrate (5 x 10(-4) M) rapidly agglutinated protoplasts and protected them from rupture by the lytic agents. Similar studies with 0.001 to 0.004 M Mg(++) showed varying degrees of protection, which, in most cases, was only temporary. Steroidal lysis did not appear to be related to chelation, since ethylenediaminetetraacetate did not cause lysis alone and antagonized some lytic compounds. Lecithin, Tween 80, Tween 20, and Span 20 at 0.05% exhibited certain effects on protoplast stability. Span 20 strongly prevented lysis by steroids. Tween 20 alone quickly caused protoplast rupture. Lecithin and Tween 80, which also caused lysis alone, interfered with lytic steroids and CPC. The test compounds were both inhibitory and lethal to cells of Sarcina lutea. The results suggest that direct action on cell membranes may be chiefly responsible for the antimicrobial properties of the steroids. 相似文献
7.
An application of the agargel precipitin-inhibition technique of Ray and Kadull detects the C-reactive protein present in the acute-phase human sera. The sensitivity of this procedure is compared with the capillary tube-precipitin method of Selman and Halpern. 相似文献
8.
Agar-Gel Precipitin-Inhibition Technique for C-Reactive Protein Determinations: III. Quantitation of C-Reactive Protein in Serum Specimens
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A quantitative C-reactive protein serological procedure has been developed. By use of this method, which is performed in agar-gel plates, from 2 to 654 μg of C-reactive protein per ml of titrated human serum can be detected. The method is based on the inhibition of a specific C-reactive protein antigen-antibody precipitate formed in agar-gel by the minimal reactive dilutions of each reagent in 48 hr. It is simple, sensitive, and readily reproducible. 相似文献
9.
We isolated from a HeLa genomic library 38 plaques that hybridized to total mitochondrial (mt) DNA isolated from human placenta. One clone (HLmt-17.8) hybridized to a 740 base-pair (12 S ribosomal RNA gene and displacement loop) mtDNA probe and was characterized in more detail. Within its 17.8 x 10(3) base-pair insert a 1.6 x 10(3) base-pair mtDNA fragment was similar to three non-sequential coding genes of human mtDNA, including a part of the 12 S ribosomal RNA (684-971), the cytochrome oxidase I (6553-7302), and two NADH dehydrogenase [ND4L/ND4] (10,606-11,159). The similarity to human mtDNA sequences was 92.0%, 92.3% and 92.4%, respectively, the highest degree of similarity to human mtDNA so far reported. This is also the first report of several adjacent mtDNA-like sequences in cellular chromosomes. The mtDNA-like sequences in HLmt-17.8 was found in the DNAs of human placenta, freshly isolated human leukocytes, foreskin and several human cell lines; but it was not present in other primates or lower organisms. The HLmt-17.8 mtDNA-like region appears to be a pseudogene that transferred into the nucleus in humans more recently than nine million years ago. 相似文献
10.
G. Shay Fout Jennifer L. Cashdollar Eunice A. Varughese Sandhya U. Parshionikar Ann C. Grimm 《Journal of visualized experiments : JoVE》2015,(97)
EPA Method 1615 was developed with a goal of providing a standard method for measuring enteroviruses and noroviruses in environmental and drinking waters. The standardized sampling component of the method concentrates viruses that may be present in water by passage of a minimum specified volume of water through an electropositive cartridge filter. The minimum specified volumes for surface and finished/ground water are 300 L and 1,500 L, respectively. A major method limitation is the tendency for the filters to clog before meeting the sample volume requirement. Studies using two different, but equivalent, cartridge filter options showed that filter clogging was a problem with 10% of the samples with one of the filter types compared to 6% with the other filter type. Clogging tends to increase with turbidity, but cannot be predicted based on turbidity measurements only. From a cost standpoint one of the filter options is preferable over the other, but the water quality and experience with the water system to be sampled should be taken into consideration in making filter selections. 相似文献