全文获取类型
收费全文 | 1077篇 |
免费 | 58篇 |
国内免费 | 4篇 |
专业分类
1139篇 |
出版年
2023年 | 15篇 |
2022年 | 30篇 |
2021年 | 40篇 |
2020年 | 26篇 |
2019年 | 48篇 |
2018年 | 42篇 |
2017年 | 29篇 |
2016年 | 50篇 |
2015年 | 53篇 |
2014年 | 68篇 |
2013年 | 86篇 |
2012年 | 83篇 |
2011年 | 80篇 |
2010年 | 27篇 |
2009年 | 44篇 |
2008年 | 43篇 |
2007年 | 46篇 |
2006年 | 45篇 |
2005年 | 37篇 |
2004年 | 24篇 |
2003年 | 33篇 |
2002年 | 25篇 |
2001年 | 15篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1974年 | 3篇 |
1972年 | 10篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1966年 | 3篇 |
排序方式: 共有1139条查询结果,搜索用时 15 毫秒
91.
92.
Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption. 相似文献
93.
Malkeet Singh Bahia Shravan Kumar Gunda Shwetha Reddy Gade Saikh Mahmood Ravikumar Muttineni Om Silakari 《Journal of molecular modeling》2011,17(1):9-19
Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting
enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses
has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify the most important features
impacting TACE inhibitory activity of ANTs. The CoMSIA model resulted to be slightly more predictive than CoMFA model, and
gave conventional r2 0.991, rcv2 0.793, q2 0.777, SEE 0.050, F-value 655.610, and rtest2 0.871. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These
studies will be useful to design new TACE inhibitors with improved potency. 相似文献
94.
CYP1A1 is the phase I enzyme that detoxifies the carcinogen or converts it into a more electrophilic form, metabolized by phase II enzymes like GSTP1. These detoxifying genes have been extensively studied in association with head and neck cancer (HNC) in different ethnic groups worldwide. The current study was aimed at screening genetic polymorphisms of genes CYP1A1 and GSTP1 in 388 Pakistani HNC patients and 150 cancer-free healthy controls, using PCR-SSCP. No already known variants of either gene were found, however a novel frameshift mutation due to insertion of T (g.2842_2843insT) was observed in the CYP1A1 gene. A statistically significant number (5.4%) of HNC cases, with the mean age of 51.75 (±15.7) years, presented this frameshift mutation in the conserved domain of CYP1A1. Another novel substitution mutation in was found in the GSTP1 gene, presenting TA instead of AG. The g.2848A > T polymorphism causes a leucine-to-leucine formation, whereas g.2849G > A causes alanine-to-threonine formation at amino acid positions 166 and 167, respectively. These exonic mutations were found in 9.5% of the HNC patients and in none of the controls. In addition, two intronic deletions of C (g.1074delC and g.1466delC) were also found in 11 patients with a mean age of 46.2 (±15.6) years. In conclusion, accumulation of mutations in genes CYP1A1 and GSTP1 appears to be associated with increased risk of developing HNC, suggesting that mutations in these genes may play a role in the etiology of head and neck cancer. 相似文献
95.
Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain inter- actions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as "interacting". In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis ele- gans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area un- der the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs in- creased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on aver- age 4 times better than those predicted by either phylogenetic profiling or gene expression profiling. 相似文献
96.
Dextransuccrase (E.C 2.4.1.5) is a key enzyme in S. mutans for the metabolism of sucrose which helps in the adherence and accumulation of bacteria on tooth surface leading to the formation of dental caries. Dextransuccrase resembles in its catalytic properties with the brush boarder sucrase and exhibits pH dependent inhibitory and stimulatory effects in response to Na+. In this communication we studied the effect of monovalent cations on the activity of dextransuccrase from S. mutans. The percentage inhibition of dextransuccrase was 65% at 0.5 mM NaCl which enhanced to 90% at 20 mM sodium concentration. However there was no effect on dextransucrase activity in presence of other monovalent cations (Rb+, Cs+, and K+) tested. Enzyme activity was enhanced 20–24% in acidic pH but was strongly inhibited (59–89%) around neutral and alkaline pH by 0.5–2.0 mM sodium chloride. Upon dialysis, 86% of enzyme activity was restored to control values. There was no effect of 2 mM NaCl on glucosyltransferase activity of the enzyme. Kinetic studies revealed that enzyme showed biphasic effects in response to Na+ ions. At acidic pH the enzyme exhibited mixed type of activation affecting both Vmax and Km, while in alkaline pH, the enzyme showed V- type effect reducing Vmax by 74% without affecting Km. The effects of sodium ions on dextransuccrase activity were specific, thus it can be useful to block its catalytic activity, and reducing the cariogenic potential of S. mutans. 相似文献
97.
98.
Umair Mahmood Muhammad Imran Salma Iqbal Naik Huma Arshad Cheema Anjum Saeed Muhammad Arshad Saqib Mahmood 《Gene》2012
Type I galactosemia is an inborn error resulting from mutations on both alleles of the GALT gene, which leads to the absence or deficiency of galactose-1-phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the conversion of galactose into glucose. On the basis of residual GALT activity, Type I galactosemia is classified into severe “Classical” and mild “Duarte” phenotypes. Classical galactosemia is frequently associated with S135L, Q188R and K285N mutations in the GALT gene. The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations. The present study aimed at detecting S135L, Q188R and K285N mutations and the N314D variant in the GALT gene by PCR using amplification refractory mutation system (ARMS). ARMS assays were established using standard DNA samples and were used for 8 galactosemia patients and 190 unrelated normal subjects all of Pakistani origin. S135L and K285N mutations were present neither in galactosemia patients nor in normal subjects. Only one galactosemia patient carried Q188R mutation that was in homozygous state. However, the N314D variant was frequently found both in affected (7 out of 16 alleles) and normal subjects (55 out of 380 alleles). This finding indicates that Duarte allele D314 might be far more common in Pakistani population than in European and North American ones. 相似文献
99.
Debra?L.?Abercrombie Shelley?C.?Clarke Mahmood?S.?ShivjiEmail author 《Conservation Genetics》2005,6(5):775-788
The future status of sharks is an issue of widespread conservation concern due to declines in many species in the face of
high levels of exploitation to satisfy market demands for products, especially fins. Substantial declines in the large-bodied
hammerhead sharks, Sphyrna lewini, S. mokarran and S. zygaena, even in regions where some management occurs, indicate that informed conservation measures are warranted for these circumglobally
distributed species. Despite the importance of assessing shark catch and trade on a species-specific basis to detect potential
overexploitation of individual species, achieving this goal for hammerheads has proven elusive due to difficulties in identification
of their products. Here, we present the development and application of a diagnostic, streamlined, five-primer multiplex polymerase
chain reaction assay utilizing species-specific primers based on nuclear ribosomal ITS2 for the three hammerhead species throughout
their global distribution. Application of this assay to investigations of the fin market confirmed the presence of hammerhead
fins in the international trade. A study of the world’s largest fin market in Hong Kong revealed a high concordance between
specific Chinese-name trade categories and fins from these three species (“Bai Chun” with S. lewini, “Gui Chun” with S. zygaena and “Gu Pian” with S.␣mokarran), and clear species preferences. This concordance information allows the use of market records for monitoring species-specific
trends in trade and exploitation rates. The assay is also proving useful for identification of shark body parts in U.S. fisheries
law-enforcement activities. Screening of morphologically identified “ S. lewini” from globally distributed areas using this assay with subsequent whole ITS2 sequencing suggests a cryptic species closely
related to S. lewini occurs off the SE USA coast. 相似文献
100.
Mahmood S.?ShivjiEmail author Demian D.?Chapman Ellen K.?Pikitch Paul W.?Raymond 《Conservation Genetics》2005,6(6):1035-1039
Great white sharks are protected by national legislation in several countries, making this species the most widely protected
elasmobranch in the world. Although the market demand for shark fins in general has continued to grow, the value and extent
of utilization of white shark fins in trade has been controversial. We combine law enforcement with genetic profiling to demonstrate
that illegal trade in fins of this species is occurring in the contemporary international market. Furthermore, we document
the presence of fins from very young white sharks in the trade, suggesting a multiple-use market (food to trophies) exists
for fins of this species. The presence of small fins in the trade contradicts the view that white shark fins have market value
only as large display trophies, and not as food. Our findings indicate that effective conservation of protected shark species
will require international management regimes that include monitoring of the shark fishery and trade on a species-specific
basis. 相似文献