全文获取类型
收费全文 | 1804篇 |
免费 | 156篇 |
国内免费 | 2篇 |
出版年
2022年 | 12篇 |
2021年 | 37篇 |
2020年 | 15篇 |
2019年 | 22篇 |
2018年 | 32篇 |
2017年 | 28篇 |
2016年 | 44篇 |
2015年 | 74篇 |
2014年 | 84篇 |
2013年 | 101篇 |
2012年 | 126篇 |
2011年 | 119篇 |
2010年 | 71篇 |
2009年 | 63篇 |
2008年 | 92篇 |
2007年 | 98篇 |
2006年 | 85篇 |
2005年 | 74篇 |
2004年 | 76篇 |
2003年 | 72篇 |
2002年 | 77篇 |
2001年 | 17篇 |
2000年 | 20篇 |
1999年 | 22篇 |
1998年 | 25篇 |
1997年 | 13篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 9篇 |
1993年 | 18篇 |
1992年 | 22篇 |
1991年 | 21篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 15篇 |
1987年 | 14篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 18篇 |
1983年 | 21篇 |
1982年 | 16篇 |
1981年 | 13篇 |
1980年 | 21篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1976年 | 18篇 |
1975年 | 11篇 |
1974年 | 14篇 |
1973年 | 10篇 |
排序方式: 共有1962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.
Sergio Cardoso Laura Valverde Miguel A. Alfonso-Sánchez Leire Palencia-Madrid Xabier Elcoroaristizabal Jaime Algorta Susana Catarino David Arteta Rene J. Herrera María Teresa Zarrabeitia José A. Pe?a Marian M. de Pancorbo 《PloS one》2013,8(7)
The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations. 相似文献
3.
Legionella pneumophila in Cooling Towers: Fluctuations in Counts, Determination of Genetic Variability by Pulsed-Field Gel Electrophoresis (PFGE), and Persistence of PFGE Patterns
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)
Sonia Ragull Marian Garcia-Nuez Maria Luisa Pedro-Botet Nieves Sopena Maria Esteve Rafael Montenegro Miquel Sabri 《Applied microbiology》2007,73(16):5382-5384
The concentrations of Legionella pneumophila in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time. 相似文献
4.
5.
Marian Irwin 《The Journal of general physiology》1922,5(2):223-224
1. An accurate quantitative method of measuring the penetration of dye into the living cell is described. 2. Cresyl blue is unable to penetrate rapidly unless the pH outside the cell is decidedly greater than that inside. The rate of penetration increases with increasing pH. 3. Around pH 9 penetration of the dye is rapid while the reverse is true of exosmosis. At low pH values (5.9) exosmosis is rapid and penetration is very slow. 相似文献
6.
Dan Cog?lniceanu Laurentiu Rozylowicz Paul Székely Ciprian Samoil? Florina St?nescu Marian Tudor Diana Székely Ruben Iosif 《ZooKeys》2013,(341):49-76
The reptile fauna of Romania comprises 23 species, out of which 12 species reach here the limit of their geographic range. We compiled and updated a national database of the reptile species occurrences from a variety of sources including our own field surveys, personal communication from specialists, museum collections and the scientific literature. The occurrence records were georeferenced and stored in a geodatabase for additional analysis of their spatial patterns. The spatial analysis revealed a biased sampling effort concentrated in various protected areas, and deficient in the vast agricultural areas of the southern part of Romania. The patterns of species richness showed a higher number of species in the warmer and drier regions, and a relatively low number of species in the rest of the country. Our database provides a starting point for further analyses, and represents a reliable tool for drafting conservation plans. 相似文献
7.
M Orlowski 《Biochemistry》1990,29(45):10289-10297
8.
Effect of Bacteriophage on Colonization of Sugarbeet Roots by Fluorescent Pseudomonas spp 总被引:2,自引:1,他引:1
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)
The colonization potential of two fluorescent Pseudomonas strains (M11/4, B2/6) that exhibit antifungal activity in vitro was studied on the roots of sugarbeet plants in a clay loam soil. The cell density of the introduced bacteria declined on the root system over a 16-day test period in nonsterile soil. Strain B2/6 declined at a significantly faster rate compared with M11/4. This loss in viability and difference in colonization ability between M11/4 and B2/6 was not observed in sterile soil. Nutrient deprivation induced by indigenous microorganisms was excluded as a key factor involved in the decline of the introduced bacteria on the basis that strains M11/4 and B2/6 retained viability when subjected to nutrient starvation conditions over a 16-day period. Experiments designed to test whether antagonism by indigenous microorganisms was responsible for the decline in the introduced fluorescent Pseudomonas sp. population revealed the presence of large numbers of bacteriophage in the soil capable of lysing strain B2/6. Reconstitution experiments carried out with sugarbeet seedlings inoculated independently with strains M11/4 and B2/6 and grown in sterile soil to which a soil phage filtrate had been added showed a significant decrease in the viability of strain B2/6 relative to M11/4. Phage antagonistic toward strain B2/6 were detected in 43% of soils taken from the major sugarbeet growing regions of Ireland. 相似文献
9.
Regulation of Trichodiene Synthase in Fusarium sporotrichioides and Gibberella pulicaris (Fusarium sambucinum) 总被引:5,自引:3,他引:2
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)
The regulation of trichodiene synthase (TS) and its relationship to trichothecene biosynthesis was investigated in Fusarium sporotrichioides NRRL 3299 and Gibberella pulicaris R-6380. Cultures were analyzed for the presence of TS activity, trichothecenes, and immunodetectable TS polypeptide over a time period of 144 h. Enzyme activity increased from barely detectable to maximum levels over a period of 3 h for F. sporotrichioides, while in G. pulicaris, a steady increase was observed over 144 h. Increases in TS activity of 50-fold for F. sporotrichioides and 10-fold for G. pulicaris R-6380 preceded by several hours the detection of trichothecenes. Immunoblot analysis employing polyclonal serum specific for the enzyme from F. sporotrichioides showed that increases in the levels of TS polypeptide corresponded to the observed changes in enzyme activity for both organisms. These data indicate that the regulation of TS activity is accomplished through increases in its cellular concentration and that TS may serve as a useful indicator of trichothecene biosynthetic activity. 相似文献
10.
Membrane solubilization by detergent: use of brominated phospholipids to evaluate the detergent-induced changes in Ca2+-ATPase/lipid interaction 总被引:1,自引:0,他引:1
B de Foresta M le Maire S Orlowski P Champeil S Lund J V M?ller F Michelangeli A G Lee 《Biochemistry》1989,28(6):2558-2567
The solubilization and delipidation of sarcoplasmic reticulum Ca2+-ATPase by different nonionic detergents were measured from changes in turbidity and recovery of intrinsic fluorescence of reconstituted ATPase in which tryptophan residues had been quenched by replacement of endogenous phospholipids with brominated phospholipids. It was found that incorporation of C12E8 or dodecyl maltoside (DM) at low concentrations in the membrane, resulting in membrane "perturbation" without solubilization, displaced a few of the phospholipids in contact with the protein; perturbation was evidenced by a parallel drop in ATPase activity. As a result of further detergent addition leading to solubilization, the tendency toward delipidation of the immediate environment of the protein was stopped, and recovery of enzyme activity was observed, suggesting reorganization of phospholipid and detergent molecules in the solubilized ternary complex, as compared to the perturbed membrane. After further additions of C12E8 or DM to the already solubilized membrane, the protein again experienced progressive delipidation which was only completed at a detergent concentration about 100-fold higher than that necessary for solubilization. Delipidation was correlated with a decrease in enzyme activity toward a level similar to that observed during perturbation. On the other hand, Tween 80, Tween 20, and Lubrol WX failed to solubilize SR membranes and to induce further ATPase delipidation when added after preliminary SR solubilization by C12E8 or dodecyl maltoside. For Tween 80, this can be related to an inability to solubilize pure lipid membrane; in contrast, Tween 20 and Lubrol WX were able to solubilize liposomes but not efficiently to solubilize SR membranes. In all three cases, insertion of the detergent in SR membranes is, however, demonstrated by perturbation of enzyme activity. Correlation between detergent structure and ability to solubilize and delipidate the ATPase suggests that one parameter impeding ATPase solubilization might be the presence of a bulky detergent polar headgroup, which could not fit close to the protein surface. We also conclude that in the active protein/detergent/lipid ternary complexes, solubilized by C12E8 or dodecyl maltoside, most phospholipids remain closely associated with the ATPase hydrophobic surface as in the membranous form. Binding of only a few detergent molecules on this hydrophobic surface may be sufficient for inhibition of ATPase activity observed at high ATP concentration, both during perturbation and in the completely delipidated, solubilized protein.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献