全文获取类型
收费全文 | 192篇 |
免费 | 12篇 |
专业分类
204篇 |
出版年
2021年 | 4篇 |
2020年 | 2篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 7篇 |
2013年 | 13篇 |
2012年 | 9篇 |
2011年 | 10篇 |
2010年 | 12篇 |
2009年 | 14篇 |
2008年 | 9篇 |
2007年 | 7篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1946年 | 1篇 |
排序方式: 共有204条查询结果,搜索用时 11 毫秒
1.
Genetic heterogeneity in tuberous sclerosis 总被引:8,自引:0,他引:8
L A Janssen L A Sandkuyl E C Merkens J A Maat-Kievit J R Sampson P Fleury R C Hennekam G C Grosveld D Lindhout D J Halley 《Genomics》1990,8(2):237-242
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23. 相似文献
2.
3.
4.
Characterization of four human YAC libraries for clone size, chimerism and X chromosome sequence representation. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R Nagaraja J Kere S MacMillan M J Masisi D Johnson B J Molini G R Halley K Wein M Trusgnich B Eble 《Nucleic acids research》1994,22(16):3406-3411
Four collections of human X-specific YACs, derived from human cells containing supernumerary X chromosomes or from somatic cell hybrids containing only X human DNA were characterized. In each collection, 80-85% of YAC strains contained a single X YAC. Five thousand YACs from the various libraries were sized, and cocloning was assessed in subsets by the fraction of YAC insert-ends with non-X sequences. Cocloning was substantial, ranging up to 50% for different collections; and in agreement with previous indications, in all libraries the larger the YACs, the higher the level of cocloning. In libraries made from human-hamster hybrid cells, expected numbers of clones were recovered by STS-based screening; but unexpectedly, the two collections from cells with 4 or 5 X chromosomes yielded numbers of YACs corresponding to an apparent content of only about two X equivalents. Thus it is possible that the DNA of inactive X chromosomes is poorly cloned into YACs, speculatively perhaps because of its specialized chromatin structure. 相似文献
5.
Sonja Buyle Edwin Reyniers Lieve Vits Kristel De Boulle Ingrid Handig Floris L. E. Wuyts Wout Deelen Dicky J. J. Halley Ben A. Oostra Patrick J. Willems 《Human genetics》1993,92(3):269-272
For many years, the high prevalence of the fragile X syndrome was thought to be caused by a high mutation frequency. The recent isolation of the FMR1 gene and identification of the most prevalent mutation enable a more precise study of the fragile X mutation. As the vast majority of fragile X patients show amplification of an unstable trinucleotide repeat, DNA studies can now trace back the origin of the fragile X mutation. To date, de novo mutations leading to amplification of the CGG repeat have not yet been detected. Recently, linkage disequilibrium was found in the Australian and US populations between the fragile X mutation and adjacent polymorphic markers, suggesting a founder effect of the fragile X mutation. We present here a molecular study of Belgian and Dutch fragile X families. No de novo mutations could be found in 54 of these families. Moreover, we found significant (P < 0.0001) linkage disequilibrium in 68 unrelated fragile X patients between the fragile X mutation and an adjacent polymorphic microsatellite at DXS548. This suggests that a founder effect of the fragile X mutation also exists in the Belgian and Dutch populations. Both the absence of new mutations and the presence of linkage disequilibrium suggest that a few ancestral mutations are responsible for most of the patients with fragile X syndrome. 相似文献
6.
Comparison of the alpha-mannosidases in fibroblast cultures from patients with mannosidosis and mucolipidosis II and from controls. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D J Halley B G Winchester L J Burditt A d''Azzo D Robinson H Galjaard 《The Biochemical journal》1980,187(2):541-543
Normal human spleen contains two forms of membrane-bound beta-glucosidase, distinguishable by their thermostability and kinetic properties. The spleen from a patient with adult Gaucher's disease was deficient in the major, thermolabile, form of the enzyme. 相似文献
7.
Correction of I-cell defect by hybridization with lysosomal enzyme deficient human fibroblasts
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A. d'Azzo D. J. J. Halley A. Hoogeveen H. Galjaard 《American journal of human genetics》1980,32(4):519-528
I-cell fibroblasts with a multiple intracellular lysosomal enzyme deficiency were hybridized with cells from patients with different types of single lysosomal enzyme defects. Fusion with GM2 gangliosidosis, type 2, (Sandhoff disease) fibroblasts resulted in a restoration of the hexosaminidase activity, in a normalization of the electrophoretic mobility of the isoenzymes, and in a decreased activity in the medium. Fusion of I-cells with fibroblasts from GM1 gangliosidosis, type 1, led to enhancement of β-galactosidase (β-gal) activity. This complementation must be the result of the presence of normal polypeptide chains in I-cells, whereas the other cell types provide a factor that causes the intracellular retention of the enzymes. Restoration of β-gal was also observed in heterokaryons after fusion of I-cells with β-galactosidase/neuraminidase-deficient (β-gal−/neur−) variants, indicating that the neuraminidase(s) and the posttranslational modification of β-gal are affected in a different way in I-cell disease and in β-gal−/neur− variants. Fusion of I-cells with mannosidosis fibroblasts resulted in a restoration of the acidic form of α-mannosidase and in a decrease of the extracellular activity of both this enzyme and the hexosaminidase enzyme, indicating that fusion of I-cells with different types of fibroblasts with a single lysosomal enzyme deficiency not only leads to complementation for one particular enzyme but also to a correction of the basic defect in I-cells. 相似文献
8.
Nonsurgical recoveries and transfers of embryos were performed at the McKellar Embryo Transplant Center from 122 superovulated Brahman cows. FSH-P (Armour) was used to superovulate all cows at dose levels ranging from 36 to 48 mg total FSH-P. Luteal regression was induced by use of 40 mg PGF(2(alpha)) in all 122 cows. Embryos were transferred into recipients 6, 7 or 8 days after observed estrus. Embryos were successfully collected from 82% of the FSH-P treated cows. The dose level of FSH-P affected numbers of embryos collected (P<.05). Numbers of embryos collected from cows superovulated with 36-38, 40, 42, 43, 44, 45, 46 and 47-48 mg FSH-P were 2.8 +/- 1.0, 6.8 +/- 1.1, 9.4 +/- 1.4, 10.0 +/- 2.7, 7.1 +/- 1.6, 6.8 +/- 2.0, 5.0 +/- 1.7 and 4.6 +/- 2.0 embryos, respectively. The dose level of FSH-P also affected numbers of embryos transferred (P<.10). Number of embryos transferred from cows superovulated with 36-38, 40, 42, 43, 44, 45, 46 and 47-48 mg FSH-P were 2.8 +/- 1.9, 5.2 +/- 0.9, 6.9 +/- 1.2, 6.7 +/- 2.1, 4.8 +/- 1.3, 5.1 +/- 1.4, 3.4 +/- 1.2 and 3.2 +/- 2.1 embryos, respectively. The developmental stage (D) of the embryo was also a factor in pregnancy rate of recipients (morula = 13.8%, blastocyst = 22.1% and expanded blastocyst = 29.9%; P<.005). The skill of the technician (T) transferring the embryo had a dramatic effect upon subsequent pregnancy rate of the recipients (T 1 = 46.0% vs T 2 = 22.6% pregnancy rate; P<.005). Pregnancy rate of recipients was also affected by the stage postestrus (S) at which the embryo was transferred (day 6 = 23.5%, day 7 = 25.5% and day 8 = 42.3% pregnancy rate; P<.05). Interactions were found between T x S, T x D, S x D and T x S x D (P<.05). These data indicate that use of 40, 42, or 43 mg total doses of FSH-P were quite effective in superovulating the Brahman cow. Recipients transferred on day 8 postestrus achieved higher pregnancy rates than recipients transferred on days 6 or 7 postestrus. Embryos transferred in the expanded blastocyst stage of development proved to yield the highest pregnancy rates in recipients. 相似文献
9.
A Reuser D Halley E de Wit A Hoogeveen M van der Kamp M Mulder H Galjaard 《Biochemical and biophysical research communications》1976,69(2):311-318
Intercellular exchange of N-acetyl-β-D-glucosaminidase (EC 3.2.1.30) β-galactosidase (EC 3.2.1.23) and acid α-glucosidase (EC 3.2.1.20) was studied after cocultivation of normal and enzyme deficient human fibroblasts in confluent cultures. Enzyme activities were measured in single cells using microchemical procedures. After co-cultivation of normal control fibroblasts and those from a patient with Sandhoff's disease an increase of activity of N-acetyl-β-D-glucosaminidase was found in Sandhoff cells, together with a decrease of activity in normal control cells. After co-cultivation of normal fibroblasts and those from patients with glycogenosis II and GM1-gangliosidosis, no indication was found for intercellular transfer of acid α-glucosidase and β-galactosidase respectively. The significance of the results is discussed in respect of the hypothesis of Hickman and Neufeld about secretion and uptake of lysosomal enzymes. 相似文献
10.
Helen R. P. Phillips John M. Halley J. Nicolas Urbina‐Cardona Andy Purvis 《Ecography》2018,41(7):1220-1231
Habitat fragmentation accompanies habitat loss, and drives additional biodiversity change; but few global biodiversity models explicitly analyse the effects of both fragmentation and loss. Here we propose and test the hypothesis that, as fragment area increases, species density (the number of species in a standardised plot) will scale with an exponent given by the difference between the exponents of the species–area relationships for islands (z ~ 0.25) and in contiguous habitat (z ~ 0.15), and test whether scaling varies between land uses. We also investigate the scaling of overall abundance and rarefaction‐based richness, as some mechanisms make different predictions about how fragment area should affect them. The relevant data from the taxonomically and geographically broad PREDICTS database were used to model the three diversity measures, testing their scaling with fragment area and whether the scaling exponent varied among land uses (primary forest, secondary forest, plantation forest, cropland and pasture). In addition, the consistency of the response of species density to fragment area was tested across three well represented taxa (Magnoliopsida, Hymenoptera and ‘herptiles’). Species density and total abundance showed area‐scaling exponents of 0.07 and 0.16, respectively, and these exponents did not vary significantly among land uses; rarefaction‐based richness by contrast did not increase consistently with area. These results suggest that the area‐scaling of species density is driven by the area‐scaling of total abundance, with additive edge effects (species moving into the small fragments from the surroundings) opposing – but not fully overcoming – the effect of fragment area on overall density of individuals. The interaction between fragment area and higher taxon (plants, vertebrates and invertebrates), which remained in the rarefied richness model, indicates that mechanisms may vary among groups. 相似文献