全文获取类型
收费全文 | 666篇 |
免费 | 82篇 |
国内免费 | 3篇 |
出版年
2022年 | 6篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 23篇 |
2014年 | 22篇 |
2013年 | 27篇 |
2012年 | 40篇 |
2011年 | 32篇 |
2010年 | 13篇 |
2009年 | 25篇 |
2008年 | 27篇 |
2007年 | 31篇 |
2006年 | 23篇 |
2005年 | 38篇 |
2004年 | 34篇 |
2003年 | 25篇 |
2002年 | 22篇 |
2001年 | 15篇 |
2000年 | 17篇 |
1999年 | 21篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 15篇 |
1986年 | 13篇 |
1985年 | 8篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 14篇 |
1977年 | 7篇 |
1974年 | 7篇 |
1973年 | 8篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1967年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有751条查询结果,搜索用时 15 毫秒
11.
Edith Coonen Joyce C. Harper Frans C. S. Ramaekers Joy D. A. Delhanty Anton H. N. Hopman Joep P. M. Geraedts Alan H. Handyside 《Human genetics》1994,94(6):609-615
The extent of chromosomal mosaicism in human preimplantation embryos was examined using an improved procedure for the preparation and spreading of interphase nuclei for use in fluorescence in situ hybridisation, allowing the analysis of every nucleus within an embryo. One cell showed no hybridisation signals in only three of the 38 embryos that were included in this study, i.e. the hybridisation efficiency per successfully spread nucleus was 99% (197/200). Double-target in situ hybridisation analyses with X- and Y-chromosome-specific probes was performed to analyse nine embryos resulting from normal fertilisation, 22 polypronucleate embryos and seven cleavage-stage embryos where no (apronucleate) or only one pronucleus (monopronucleate) was observed. We also analysed autosomes 1 and 7 by double-target in situ hybridisation in the nuclei of two apronucleate, one monopronucleate and four polypronucleate embryos. All nine embryos that resulted from normal fertilisation were uniformly XY or XX. None of the apronucleate or monopronucleate embryos was haploid: three were diploid, one was triploid and three were mosaic. Fertilisation was detected by the presence of a Y-specific signal in four of these embryos. Of the polypronucleate embryos, two were diploid, two were triploid and 18 were mosaic for the sex chromosomes and/or autosomes 1 and 7. These results demonstrate that fertilisation sometimes occurs in monopronucleate embryos and that chromosomal mosaicism can be detected with high efficiency in apronucleate, monopronucleate and polypronucleate human embryos using fluorescence in situ hybridisation. 相似文献
12.
Henk Meijer Roselie J. E. Jongbloed M. Hekking Leo J. M. Spaapen Joep P. M. Geraedts 《Human genetics》1993,92(6):588-592
Restriction fragment length polymorphism haplotyping of mutated and normal phenylalanine hydroxylase (PAH) alleles in 49 Dutch phenylketonuria (PKU) families was performed. All mutant PAH chromosomes identified by haplotyping (n = 98) were screened for eight of the most predominant mutations. Compound heterozygosity was proven in 40 kindreds. Homozygosity was found for the IVS12nt1 mutation in 5 families, and for the R158Q and IVS10nt546 mutations in one family each. All patients from these families suffer from severe PKU, providing additional proof that these mutations are deleterious for the PAH gene. Genotypical heterogeneity was evident for mutant haplotype 1 (n = 27) carrying the mutations R261Q (n = 12), E280K (n = 4), P281L (n = 1) and unknown (n = 10), and likewise for mutant haplotype 4 (n = 30) carrying the mutations R158Q (n = 13), Y414C (n = 1) and unknown (n = 16). Mutant haplotype 3 (n = 20), in tight association with mutation IVS12nt1, appeared to be in strong linkage disequilibrium (LDE) with its normal counterpart allele (n = 4). Mutant haplotype 6 (n = 4), in tight association with the IVS10nt546 mutation, showed moderate LDE with its counterpart allele (n = I). The distribution of the mutant PAH haplotypes 1, 3 and 4 among the Dutch PKU population resembles that in other Northern and Western European countries, but it is striking that mutant haplotype 2 and its associated mutation R408W is nearly absent in The Netherlands, in strong contrast to its neighbouring countries. 相似文献
13.
Isabela Tagomori Vassilis Daioglou Pedro Rochedo Gerd Angelkorte Roberto Schaeffer Detlef van Vuuren Alexandre Szklo 《Global Change Biology Bioenergy》2023,15(2):116-127
Bioenergy could play a major role in decarbonizing energy systems in the context of the Paris Agreement. Large-scale bioenergy deployment could be related to sustainability issues and requires major infrastructure investments. It, therefore, needs to be studied carefully. The Bioenergy and Land Optimization Spatially Explicit Model (BLOEM) presented here allows for assessing different bioenergy pathways while encompassing various dimensions that influence their optimal deployment. In this study, BLOEM was applied to the Brazilian context by coupling it with the Brazilian Land Use and Energy Systems (BLUES) model. This allowed investigating the most cost-effective ways of attending future bioenergy supply projections and studying the role of recovered degraded pasture lands in improving land availability in a sustainable and competitive manner. The results show optimizing for limiting deforestation and minimizing logistics costs results in different outcomes. It also indicates that recovering degraded pasture lands is attractive from both logistics and climate perspectives. The systemic approach of BLOEM provides spatial results, highlighting the trade-offs between crop allocation, land use and the logistics dynamics between production, conversion, and demand, providing valuable insights for regional and national climate policy design. This makes it a useful tool for mapping sustainable bioenergy value chain pathways. 相似文献
14.
Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels 总被引:4,自引:0,他引:4
Demetrios K. Vassilatis Keith O. Elliston Philip S. Paress Michel Hamelin Joseph P. Arena James M. Schaeffer Lex H.T. Van der Ploeg Doris F. Cully 《Journal of molecular evolution》1997,44(5):501-508
Two cDNAs, GluClα and GluClβ, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin
class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707–711, 1994). Expression studies in Xenopus oocytes showed that GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of
related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined
the nucleotide sequence of the GluClα and GluClβ genes. In an attempt to understand the evolutionary relationship of these
channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic
analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several
intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position.
Phylogenetic analyses indicate that GluClα and GluClβ form a monophyletic subbranch in the ligand-gated ion channel superfamily
and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties
similar to GluClα and GluClβ, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride
channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination
with the distinct pharmacological properties demonstrate that GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 相似文献
15.
Jos C. F. M. Dreesen Joep P. M. Geraedts John C. M. Dumoulin Johannes L. H. Evers Math H. E. C. Pieters 《Human genetics》1995,96(3):323-329
In order to approach preimplantation testing for the fragile-X syndrome, we used genotyping of the polymorphic RS46(DXS548) locus closely linked to the FMR1 gene, in single reproductive cells of females. The RS46(DXS548) amplification was adjusted to the single cell level by a two-round polymerase chain reaction (PCR) procedure. Unfertilized oocytes and extruded polar bodies were subjected to PCR. RS46(DXS548) genotyping at the single cell level was successful in 95% of the samples. In two-third of the metaphase II oocytes and first polar bodies obtained from women who were heterozygous at the RS46(DXS548) locus, both maternal RS46(DXS548) alleles were observed because of crossing over during the first meiotic division. This makes gamete selection by first polar body analysis inefficient. From the allele frequencies found in 56 unrelated individuals, a heterozygote frequency of 51% was estimated, whereas the observed heterozygote frequency was 56%. The whole PCR procedure can be performed within 16 h after blastomere biopsy. Consequently, the selection and transfer of the diagnosed embryos can be carried out within an acceptable time. Therefore, preimplantation testing for the fragile-X syndrome with the RS46(DXS548) AC-repeat may be an alternative choice for prenatal testing for those carrier females who are heterozygous (informative) at the RS46(DXS548) locus. 相似文献
16.
Gemma A.J. Kuijpers Irene G.P. Van Nooy Jan Joep H.H.M. De Pont Sjoerd L. Bonting 《生物化学与生物物理学报:生物膜》1984,774(2):269-276
The isolated rabbit pancreas secretes a fluid containing chloride and bicarbonate in about equal concentrations. Replacement of bicarbonate by acetate, phosphate or isethionate, replacement of Na+ by Li+ and addition of ouabain to the bathing medium of the pancreas inhibit the secretion of fluid, chloride and bicarbonate in a similar fashion and by maximally 100%. Replacement of chloride by isethionate inhibits fluid secretion by maximally 50%, chloride secretion by 90% and bicarbonate secretion by 20%. It is concluded that fluid secretion is based on a Na+-gradient-dependent bicarbonate influx or proton efflux in the ductular cell, and that the secretion of chloride is secondary to that of bicarbonate. 相似文献
17.
M. D. Lazar P. S. Baenziger G. W. Schaeffer 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1984,68(1-2):131-134
Summary Frequency of callus formation in wheat (Triticum aestivum L. em. Thell) anthers cultured in vitro and the frequency of subsequent plantlet formation from such calli were examined in a diallel population produced from five inbred spring wheat cultivars. Two of the five cultivars were believed to possess relatively high frequencies of response and the other three relatively low response frequencies, based on previous studies. General and specific combining abilities were estimated and found to be highly significant for both traits. Reciprocal effects were also estimated and were highly significant for both traits. Of the 25 entries, the largest mean callus formation frequency was observed on anthers of Kitt x Olaf, while the largest mean plantlet formation frequency was observed using anthers of the cultivar, Fielder. No significant correlation was observed between the two traits. Heritability estimates in the range of 0.6–0.7 suggested, however, that both traits were highly heritable, so that rapid gain from selection for these traits should be possible. Current limitations due to genetic variation in responses therefore may not constitute a major obstacle to application of in vitro techniques by wheat breeders.Scientific Article No. 3710 Contribution No. 6686 of the Maryland Agric. Exp. Stn., Dept. of Agronomy, College Park, MD 20742, and USDA-ARS, Beltsville, MD 20705, USA 相似文献
18.
J D Schaeffer K J Kim E D Crandall 《Journal of applied physiology (Bethesda, Md. : 1985)》1984,56(1):72-77
The effects of decreased temperature, metabolic inhibition, and hyposmolality on osmotically and hydrostatically driven water flux across bullfrog alveolar epithelium were studied. Lungs were isolated from double-pithed Rana catesbeiana and prepared as sacs. Either an osmotic (0.1 M raffinose) or hydrostatic (6.3-6.6 Torr) pressure gradient was imposed across the tissue. These gradients resulted in the volume flow of water from the alveolar to pleural bath. Control water flux and hydraulic conductivity were estimated from the rate of weight loss of the lung sac. Subsequently water flux and hydraulic conductivity were determined under one of the following conditions: 1) temperature of bathing solutions lowered to 2 degrees C; 2) 1 mM 2,4-dinitrophenol added to both alveolar and pleural baths, or 3) both baths changed to half-isosmotic Ringer solution. The control hydraulic conductivities for osmotic (Lpo) and hydrostatic (Lph) pressure gradients were 3.65(+/- 0.94) X 10(-12) and 2.14(+/- 0.63) X 10(-10) ml/dyn X s, respectively. Under conditions of metabolic inhibition, hyposmolality, and decreased temperature, Lph decreased by 77, 83, and 92%, and Lpo decreased by 56, 34, and 59%, respectively. These results are most consistent with the hypothesis that the decrements in hydraulic conductivity under our experimental conditions are due to epithelial cell swelling and perhaps to changes in the characteristics of the paracellular pathway. 相似文献
19.
G. W. Schaeffer 《In vitro cellular & developmental biology. Plant》1977,13(1):31-35
Summary This report describes the culture of Su/Su, Su/su and su/su tissue in vitro. High levels of auxin and low levels of cytokinin
increase growth of the cells. The cells do not need exogenous amino acids for rapid growth and the chlorophyll deficiency
cannot be overcome by amino acids. Reduced levels of auxin and sucrose enhance differentiation, whereas cysteine in the autoclaved
medium inhibit differentiation. The Su chlorophyll mutant of tobacco provides a marker for in vitro studies on photosynthesis
and photorespiration, chloroplast genetics and cell fusion techniques. 相似文献
20.
Sexually inexperienced male Wistar rats (strain WI in our colony) known to very infrequently display spontaneous lordosis behavior (Schaeffer et al., 1990b) were used. A first group was tested four times at 5-day intervals for lordosis with vigorous stimulus males (heterotypic sexual behavior), immediately following testing for masculine sexual activity with highly receptive females (homotypic sexual behavior). A small number of animals displayed lordosis during the first test, but more and more animals displayed this behavior from the first to the fourth test. There was no relationship between the degree of masculine sexual activity--intromission without ejaculation or ejaculation--and the occurrence of lordosis behavior. A second group was tested only once for both masculine sexual activity and lordosis behavior as above and afterwards three times at 5-day intervals for lordosis behavior in the absence of any previous testing for masculine sexual activity. A few animals displayed lordosis during their first test. As compared to the first group, the animals which had not displayed lordosis in the first test never showed lordosis responses in the following tests. It is concluded that both homotypic and heterotypic sexual interactions are required for the display of lordosis behavior in the strain of Wistar rats used in this study. 相似文献