全文获取类型
收费全文 | 436篇 |
免费 | 37篇 |
出版年
2023年 | 4篇 |
2021年 | 11篇 |
2020年 | 9篇 |
2019年 | 13篇 |
2018年 | 14篇 |
2017年 | 11篇 |
2016年 | 22篇 |
2015年 | 28篇 |
2014年 | 25篇 |
2013年 | 40篇 |
2012年 | 33篇 |
2011年 | 30篇 |
2010年 | 22篇 |
2009年 | 25篇 |
2008年 | 25篇 |
2007年 | 22篇 |
2006年 | 28篇 |
2005年 | 12篇 |
2004年 | 24篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有473条查询结果,搜索用时 78 毫秒
1.
Trypanosoma cruzi: 4-aminopyrazolopyrimidine in the treatment of experimental Chagas' disease 总被引:1,自引:0,他引:1
JoséLuis Avila Angela Avila Edgar Mun̄oz Héctor Monzón 《Experimental parasitology》1983,56(2):236-240
An allopurinol metabolite, 4-aminopyrazolopyrimidine, was tested on two different strains of mice (NMRI-IVIC and C57Bl/6J) that had been infected 4 days earlier with the virulent Ya strain of Trypanosoma cruzi. Low doses of 4-aminopyrazolopyrimidine (0.125-0.500 mg/kg body wt/day) for 10 days induced a significant reduction in parasitemia (direct counts and subinoculation experiments) and increased survival time (without any evidence of toxicity) compared with untreated animals. When tested in vitro, 4-aminopyrazolopyrimidine was sixfold more active than allopurinol as a trypanostatic drug. The low therapeutic doses of 4-aminopyrazolopyrimidine suggest that this drug may be useful in the treatment of acute Chagas' disease. 相似文献
2.
Membrane adenosine triphosphatase of Micrococcus lysodeikticus: effect of millimolar Mg2+ in modulating the properties of the membrane-bound enzyme 总被引:3,自引:0,他引:3 下载免费PDF全文
The latency of Micrococcus lysodeikticus membrane-bound Mg(2+)-adenosine triphosphatase (ATPase) is expressed by the ratio of its activity assayed in the presence of trypsin ("total") versus the activity assayed in absence of the protease ("basal"). By isolating membranes in the presence of variable concentrations of Mg(2+) (50 mM, 10 mM, or none) and by washing them with different Mg(2+)- and ethylenediaminetetraacetic acid-containing tris(hydroxymethyl)aminomethane-hydrochloride buffers (pH 7.5), we showed that the enzyme latency was dependent on the environmental concentration of this divalent metal ion. Mg(2+) bound to at least two classes of sites. The binding of Mg(2+) to low-affinity sites (saturation at approximately 40 mM external Mg(2+)) induced a high basal ATPase activity, whereas its binding to medium-affinity sites (saturation at about 2 mM Mg(2+)) correlated with low basal activity and a very high stimulation by trypsin. Membranes with tightly bound Mg(2+) (high affinity?) revealed an intermediate behavior for the latency of M. lysodeikticus ATPase. The Mg(2+)/Ca(2+) antagonism as activators of the membrane ATPase was not directly related to Mg(2+) binding by the membranes. The efficiency of the ATPase release from M. lysodeikticus membrane by 3 mM tris(hydroxymethyl)aminomethane-hydrochloride buffer (pH 7.5) was inversely proportional to the concentration of external and/or bound Mg(2+). Deoxycholate (DOC) (1%) solubilized the ATPase from all types of membrane. All the soluble ATPases behaved as Ca(2+)-ATPases, but the DOC-soluble fractions showed degrees of latency like those of the original membranes. The DOC-soluble ATPase preparation revealed a vesicular structure and complex protein patterns by sodium dodecyl sulfate gel electrophoresis. We propose that ATPase latency is modulated via a Mg(2+)-ATPase-membrane complex. 相似文献
3.
Yeehn Yeeh Soon Suk Kang Hye Gi Chung Mun Su Chung Myong Gi Chung 《Journal of plant research》1996,109(2):161-168
Vitex rotundifolia L.f. is a woody perennial and has sexual and asexual modes of reproduction. Allozyme study was conducted on 550 plants in
13 Korean populations. The levels of genetic variability and divergence within and among populations, respectively, are considerably
lower and higher than the mean values for woody plants with similar life history tralts. Mean percentage of polymorphic loci
(P
P), mean number of alleles per locus (A
P), and mean genetic diversity (He
P) within populations ofV. rotundifolia were: 16.7%, 1.21, and 0.047. On average, about 79% of the total variation inV. rotundifolia was common to all populations (meanG
ST=0.208). In addition, significant differences in allele frequencies among populations were found in all polymorphic loci examined
(P<0.001). On the other hand, levels of genotypic diversity within and among populations were moderate. About 44% (18/41) of
multilocus genotypes were “local genotypes” (genotypes occurring in only one population), whereas only one “widespread genotype”
(genotypes occurring in more than 75% of the populations) were detected. The mean number of multilocus genotypes per population
(G) and mean genotypic diversity index (D
G) were 8.4 and 0.74, respectively. Most common multilocus genotypes found in populations were homozygous for five polymorphic
loci. The abundance of ramets of these genets is responsible for the low levels of expected heterozygosity within populations.
The results indicate that clonal reproduction may act as an enhancer of genetic drift by reducing effective size of local
populations ofV. rotundifolia. 相似文献
4.
Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers. 相似文献
5.
Rafael Deliz-Aguirre Fakun Cao Fenja H.U. Gerpott Nichanok Auevechanichkul Mariam Chupanova YeVin Mun Elke Ziska Marcus J. Taylor 《The Journal of cell biology》2021,220(7)
A recurring feature of innate immune receptor signaling is the self-assembly of signaling proteins into oligomeric complexes. The Myddosome is an oligomeric complex that is required to transmit inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for how Myddosome proteins self-assemble and regulate intracellular signaling remains poorly understood. Here, we developed a novel assay to analyze the spatiotemporal dynamics of IL1R and Myddosome signaling in live cells. We found that MyD88 oligomerization is inducible and initially reversible. Moreover, the formation of larger, stable oligomers consisting of more than four MyD88s triggers the sequential recruitment of IRAK4 and IRAK1. Notably, genetic knockout of IRAK4 enhanced MyD88 oligomerization, indicating that IRAK4 controls MyD88 oligomer size and growth. MyD88 oligomer size thus functions as a physical threshold to trigger downstream signaling. These results provide a mechanistic basis for how protein oligomerization might function in cell signaling pathways. 相似文献
6.
Top-spray fluidized bed granulation with axial fluidization airflow from the bottom of the granulator is well-established in the pharmaceutical industry. The application of swirling airflow for fluidized bed granulation was more recently introduced. This study examined the effects of various process parameters on the granules produced by side-spray fluidized bed with swirling airflow using the central composite and Box–Behnken design of experiment. Influence of the amount of binder solution, spray rate, and distance between spray nozzle and powder bed were initially studied to establish operationally viable values for these parameters. This was followed by an in-depth investigation on the effects of inlet airflow rate, atomizing air pressure and distance between spray nozzle and powder bed on granule properties. It was found that the amount of binder solution had a positive correlation with granule size and percentage of lumps but a negative correlation with size distribution and Hausner ratio of the granules. Binder solution spray rate was also found to affect the granules size. High drug content uniformity was observed in all the batches of granules produced. Both inlet airflow rate and atomizing air pressure were found to correlate negatively with granule size and percentage of lumps but correlate positively with the size distribution of the granule produced. Percentage of fines was found to be significantly affected by inlet airflow rate. Distance between spray nozzle and powder bed generally affected the percentage of lumps. 相似文献
7.
Hairpin telomeres of bacterial linear chromosomes are generated by a DNA cutting–rejoining enzyme protelomerase. Protelomerase resolves a concatenated dimer of chromosomes as the last step of chromosome replication, converting a palindromic DNA sequence at the junctions between chromosomes into covalently closed hairpins. The mechanism by which protelomerase transforms a duplex DNA substrate into the hairpin telomeres remains largely unknown. We report here a series of crystal structures of the protelomerase TelA bound to DNA that represent distinct stages along the reaction pathway. The structures suggest that TelA converts a linear duplex substrate into hairpin turns via a transient strand-refolding intermediate that involves DNA-base flipping and wobble base-pairs. The extremely compact di-nucleotide hairpin structure of the product is fully stabilized by TelA prior to strand ligation, which drives the reaction to completion. The enzyme-catalyzed, multistep strand refolding is a novel mechanism in DNA rearrangement reactions. 相似文献
8.
9.
Nazeh M. Al-abd Mohammed A. K. Mahdy Abdulsalam M. Q. Al-Mekhlafi Georges Snounou Nazia B. Abdul-Majid Hesham M. Al-Mekhlafi Mun Y. Fong 《PloS one》2013,8(7)
Background
The accuracy of the conclusions from in vivo efficacy anti-malarial drug trials depends on distinguishing between recrudescences and re-infections which is accomplished by genotyping genes coding P. falciparum merozoite surface 1 (MSP1) and MSP2. However, the reliability of the PCR analysis depends on the genetic markers’ allelic diversity and variant frequency. In this study the genetic diversity of the genes coding for MSP1 and MSP2 was obtained for P. falciparum parasites circulating in Yemen.Methods
Blood samples were collected from 511 patients with fever and screened for malaria parasites using Giemsa-stained blood films. A total 74 samples were infected with P. falciparum, and the genetic diversity was assessed by nested PCR targeting Pfmsp1 (Block2) and Pfmsp2 (block 3).Results
Overall, 58%, 28% and 54% of the isolates harboured parasites of the Pfmsp1 K1, MAD20 and RO33 allelic families, and 55% and 89% harboured those of the Pfmsp2 FC27 and 3D7 allelic families, respectively. For both genetic makers, the multiplicity of the infection (MOI) was significantly higher in the isolates from the foothills/coastland areas as compared to those from the highland (P<0.05). Pfmsp2 had higher number of distinct allelic variants than Pfmsp1 (20 vs 11). The expected heterozygosity (HE) for Pfmsp1 and Pfmsp2 were 0.82 and 0.94, respectively. Nonetheless, a bias in the frequency distribution of the Pfmsp1 allelic variants was noted from all areas, and of those of Pfmsp2 in the samples collected from the highland areas.Conclusions
Significant differences in the complexity and allelic diversity of Pfmsp1 and Pfmsp2 genes between areas probably reflect differences in the intensity of malaria transmission. The biased distribution of allelic variants suggests that in Yemen Pfmsp1 should not be used for PCR correction of in vivo clinical trials outcomes, and that caution should be exercised when employing Pfmsp2. 相似文献10.
John Chih Mun Sha Sam Alagappasamy Subash Chandran Khin Maung Cho Biswajit Guha 《Zoo biology》2013,32(3):281-290
Surplus male proboscis monkeys at the Singapore Zoo pose a considerable problem for maintenance and maximizing of exhibition potential. In 2008, a new exhibit was constructed to house and display a group of six proboscis monkey males born in Singapore Zoo. To document and monitor the all‐male group establishment in the new exhibit, we conducted observations on intragroup interactions between the monkeys, spatial use of their new exhibit, and visitor effects on their behavior. We found contact aggressive interactions between the monkeys to be consistently lower than noncontact aggressive interactions and by week six of introduction to the new exhibit, contact aggression was almost nonevident. Affiliative interactions also developed between individuals in the group, with an interface of aggressive and socioreconcilatory behavior influenced by food competition and a dominance hierarchy. This was evident from significantly higher overall aggression and affiliation during feeding times compared to nonfeeding times, and this was reduced when food competition was mitigated by modifying the feeding regime. We measured the groups’ spatial use of the exhibit and the relation to behavior, crowd size, and density. Our results showed that the proboscis monkeys utilized the available exhibit space, were largely unaffected by visitor crowd size and density, and were able to exhibit a variety of natural behaviors, including swimming. Our accomplishment in maintaining and displaying an all‐male group of proboscis monkeys in captivity provides viable options for more comprehensive captive management and breeding programs for this endangered species. Zoo Biol. 32:281‐290, 2013. © 2012 Wiley Periodicals, Inc. 相似文献