全文获取类型
收费全文 | 226篇 |
免费 | 19篇 |
出版年
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 7篇 |
2015年 | 7篇 |
2014年 | 4篇 |
2013年 | 4篇 |
2012年 | 10篇 |
2011年 | 10篇 |
2010年 | 7篇 |
2009年 | 9篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 2篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 11篇 |
1998年 | 16篇 |
1997年 | 5篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有245条查询结果,搜索用时 218 毫秒
21.
22.
Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:15,自引:9,他引:6
The neutral theory of molecular evolution predicts that the ratio of
polymorphisms to fixed differences should be fairly uniform across a region
of DNA sequence. Significant heterogeneity in this ratio can indicate the
effects of balancing selection, selective sweeps, mildly deleterious
mutations, or background selection. Comparing an observed heterogeneity
statistic with simulations of the heterogeneity resulting from random
phylogenetic and sampling variation provides a test of the statistical
significance of the observed pattern. When simulated data sets containing
heterogeneity in the polymorphism-to-divergence ratio are examined,
different statistics are most powerful for detecting different patterns of
heterogeneity. The number of runs is most powerful for detecting patterns
containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic
is most powerful for detecting patterns in which one end of the gene has
high polymorphism and the other end has low polymorphism; and a newly
developed statistic, the mean sliding G statistic, is most powerful for
detecting patterns containing one or two peaks of polymorphism with reduced
polymorphism on either side. Nine out of 27 genes from the Drosophila
melanogaster subgroup exhibit heterogeneity that is significant under at
least one of these three tests, with five of the nine remaining significant
after a correction for multiple comparisons, suggesting that detectable
evidence for the effects of some kind of selection is fairly common.
相似文献
23.
24.
Powell NA Ciske FL Cai C Holsworth DD Mennen K Van Huis CA Jalaie M Day J Mastronardi M McConnell P Mochalkin I Zhang E Ryan MJ Bryant J Collard W Ferreira S Gu C Collins R Edmunds JJ 《Bioorganic & medicinal chemistry》2007,15(17):5912-5949
We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite. 相似文献
25.
Eight strains belonging to the Oomycete genus Phytophthora were isolated from Zostera marina (seagrass) in The Netherlands over the past 25 y. Based on morphology, isozymes, temperature-growth relationships and ITS sequences, these strains were found to belong to two different Phytophthora species. Five strains, four of them isolated from rotting seeds and one isolated from decaying plants, could not be assigned to a known species and hence belong to a new species for which we propose the name Phytophthora gemini sp. nov. Three strains were isolated from decaying plants and were identified as Phytophthora inundata, thereby expanding the known habitat range of this species from fresh to brackish-saline areas. The possible role of both Phytophthora species in the decline of Z. marina in The Netherlands and the evolutionary significance of the presence of Phytophthora species in marine environments are discussed. 相似文献
26.
David?E?Comings Thomas?JH?Chen Kenneth?BlumEmail author Julie?F?Mengucci Seth?H?Blum Brian?Meshkin 《Theoretical biology & medical modelling》2005,2(1):50
Background
Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie?Results
We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered.Conclusion
The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.27.
JH Shazia Fathima Jayaraman Selvaraj Venkatacalam Sivabalan Umapathy Vidhya Rekha Rajagopal Ponnulakshmi Veeraraghavan Vishnupriya Malathi Kullappan Radhika Nalinakumari Sreekandan Surapaneni Krishna Mohan Periyasamy Vijayalakshmi 《Bioinformation》2021,17(1):212
The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration. 相似文献
28.
Andrew C. Stelzer Richard W. Frazee Chad Van Huis Joanne Cleary Anthony W. Opipari Jr. Gary D. Glick Hashim M. Al‐Hashimi 《Biopolymers》2010,93(1):85-92
Bz‐423 is an inhibitor of the mitochondrial F1F0‐ATPase, with therapeutic properties in murine models of immune diseases. Here, we study the binding of a water‐soluble Bz‐423 analog (5‐(3‐(aminomethyl)phenyl)‐7‐chloro‐ 1‐methyl‐3‐(naphthalen‐2‐ylmethyl)‐1H‐benzo][e][1,4]diazepin‐2(3H)‐one); (1) to its target subunit on the enzyme, the oligomycin sensitivity conferring protein (OSCP), by NMR spectroscopy using chemical shift perturbation and cross‐relaxation experiments. Titration experiments with constructs representing residues 1–120 or 1–145 of the OSCP reveals that (a) 1 binds to a region of the protein, at the minimum, comprising residues M51, L56, K65, V66, K75, K77, and N92, and (b) binding of 1 induces conformational changes in the OSCP. Control experiments employing a variant of 1 in which a key binding element on the small molecule was deleted; it had no perturbational effect on the spectra of the OSCP, which indicates that the observed changes with 1 represent specific binding interactions. Collectively, these data suggest that 1 might inhibit the enzyme through an allosteric mechanism where binding results in conformational changes that perturb the OSCP‐F1 interface resulting in disrupted communication between the peripheral stalk and the F1‐domain of the enzyme. © 2009 Wiley Periodicals, Inc. Biopolymers 29: 85–92, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
29.
Background
Pancreatic-tail duct ligation (PDL) in adult rodents has been reported to induce beta cell generation and increase beta cell mass but increases in beta cell number have not been demonstrated. This study examines whether PDL increases beta cell number and whether this is caused by neogenesis of small clusters and/or their growth to larger aggregates.Methodology
Total beta cell number and its distribution over small (<50 µm), medium, large (>100 µm) clusters was determined in pancreatic tails of 10-week-old mice, 2 weeks after PDL or sham.Principal findings
PDL increased total beta cell mass but not total beta cell number. It induced neogenesis of small beta cell clusters (2.2-fold higher number) which contained a higher percent proliferating beta cells (1.9% Ki67+cells) than sham tails (<0.2%); their higher beta cell number represented <5% of total beta cell number and was associated with a similar increase in alpha cell number. It is unknown whether the regenerative process is causally related to the inflammatory infiltration in PDL-tails. Human pancreases with inflammatory infiltration also exhibited activation of proliferation in small beta cell clusters.Conclusions/significance
The PDL model illustrates the advantage of direct beta cell counts over beta cell mass measurements when assessing and localizing beta cell regeneration in the pancreas. It demonstrates the ability of the adult mouse pancreas for neogenesis of small beta cell clusters with activated beta cell proliferation. Further studies should investigate conditions under which neoformed small beta cell clusters grow to larger aggregates and hence to higher total beta cell numbers. 相似文献30.
A. van Huis G. Woldewahid K. Toleubayev & W. van der Werf 《Entomologia Experimentalis et Applicata》2008,127(2):144-156
The effect of millet, Pennisetum typhoideum Rich. (Poaceae), leaf nitrogen content on fitness parameters of the desert locust, Schistocerca gregaria Forsk. (Orthoptera: Acrididae), was studied under laboratory conditions. Locusts reared on high‐nitrogen leaves were larger, developed faster, had higher survival, reproduced more and earlier, and showed greater synchronization than those fed on low‐nitrogen leaves. Active and passive cannibalism contributed to mortality when locusts were reared on low‐nitrogen leaves, but not when reared on high‐nitrogen leaves. Elevated leaf nitrogen content of host plants increased net reproduction and intrinsic rate of increase, and lowered generation time. The findings show that nitrogen content of host plants affects the potential for population increase in the desert locust. Leaf samples of common plant species were collected in the Heliotropium arbainense (Fresen.) (Boraginaceae) and Panicum turgidum (Forssk.) (Poaceae) plant communities on the Red Sea coastal plain of Sudan during the winters of 1999 and 2000. The levels of leaf nitrogen in host plants were comparable to those in the laboratory studies and consistently higher in plant samples from the Heliotropium community than in samples from the Panicum community. Both in 1999 and 2000, locust densities were much higher in the Heliotropium than in the Panicum plant community. It should be assessed whether the desert locust would be attracted to sites where host plants have high leaf nitrogen content, as this would not only increase their fitness, but also the likelihood of gregarization and outbreaks. 相似文献