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161.
Sluan D. Lin Phil Cooper Jingly Fung Heinz-Ulrich G. Weier Edward M. Rubin 《Mammalian genome》2000,11(11):1024-1029
Genetic factors affecting postnatal γ-globin expression—a major modifier of the severity of both β-thalassemia and sickle
cell anemia—have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression
pattern equivalent to that of human γ-globin. To model the human β-cluster in mice, with the goal of screening for loci affecting
human γ-globin expression in vivo, we introduced a human β-globin cluster YAC transgene into the genome of FVB/N mice. The
β-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) γ allele, resulting in postnatal expression
of human γ-globin in transgenic mice. The level of human γ-globin for various F1 hybrids derived from crosses between the FVB/N transgenics and other inbred mouse strains was assessed. The γ-globin level
of the (C3HeB/FeJ × FVB/N)F1 transgenic mice was noted to be significantly elevated. To map genes affecting postnatal γ-globin expression, we performed
a 20-centiMorgan (cM) genome scan of a (C3HeB/FeJ × FVB/N)F1 transgenics × FVB/N backcross, followed by high-resolution marker analysis of promising loci. From this analysis we mapped
a locus within an 18-cM interval of mouse Chromosome (Chr) 1 (LOD = 4.3) that contributes 10.9% of variation in γ-globin level.
Combining transgenic modeling of the human β-globin gene cluster with quantitative trait analysis, we have identified and
mapped a murine locus that impacts on human γ-globin level in vivo.
Received: 26 January, 2000 / Accepted: 2 May 2000 相似文献
162.
Heinz-Ulrich G. Weier Daniel Polikoff John J. Fawcett Karin M. Greulich Kwang-Ho Lee Scott Cram Verne M. Chapman Joe W. Gray 《Genomics》1994,21(3)
Mouse metaphase chromosomes were purified by flow sorting from the murine fibroblast cell line Mus spretus clone 5A. We sorted chromosomes that fell into five individual peaks based on the Hoechst 33258/chromomycin A3 DNA histogram: three peaks corresponding to the least amount of DNA and two peaks representing chromosomes with the most DNA content. This is the first example of the successful application of bivariate flow karyotyping to murine chromosome sorting. We then applied primer-directed in vitro DNA amplification using the polymerase chain reaction (PCR) to generate and label larger amounts of chromosome-specific DNA. In situ hybridization showed specific binding of the PCR products to mouse chromosomes Y, 19, 18, 3, and X as well as chromosomes 1 and 2. The combination of chromosome sorting from the M. spretus cell line and PCR proved to be highly valuable for generation of pools of DNA fragments that exhibit specific binding to mouse chromosomes and can be used to identify and delineate mouse metaphase chromosomes. 相似文献
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164.
Chun-Mei Lu Johnson Kwan Adolf Baumgartner Jingly F. Weier Mei Wang Tomas Escudero Santiago Munn�� Horst F. Zitzelsberger Heinz-Ulrich G. Weier 《The journal of histochemistry and cytochemistry》2009,57(6):587-597
Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival, as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multiclone and multicolor mapping experiments do not generate additional information. Our pooling protocol, described here with examples from thyroid cancer research and PGD, accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as 3 to 4 days. (J Histochem Cytochem 57:587–597, 2009) 相似文献
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166.
Sandya Narayanswami Norman A. Doggett Lynn M. Clark Carl E. Hildebrand Heinz-Ulrich Weier Barbara A. Hamkalo 《Mammalian genome》1992,2(3):186-194
We have applied EM in situ hybridization (EMISH) and pulsed field gel electrophoresis (PFGE) to samples from diploid primary cell cultures and an established cell line to examine in detail the relative organization of the major and minor satellite DNAs and telomere sequences in the genomes of Mus domesticus and Mus spretus. EMISH localizes the Mus domesticus minor satellite to a single site at the centromere-proximal end of each chromosome. Double label hybridizations with both minor satellite and telomere probes show that they are in close proximity and possibly are linked. In fact, PFGE of M. domesticus DNA digested with Sal I and Sfi I reveals the presence of fragments which hybridize to both probes and is consistent with the physical linkage of these two sequences. The M. domesticus minor satellite is the more abundant satellite in Mus spretus. Its distribution in M. spretus is characterized by diffuse labeling with no obvious concentration near chromosome ends. In addition to this repeat the M. spretus genome contains a small amount of DNA that hybridizes to a M. domesticus major satellite probe. Unlike the M. domesticus minor satellite, it is not telomere proximal but is confined to a domain at the border of the centromere and the long arm. Thus, although both species possess all three sequences, except for the telomeres, their distribution relative to one another is not conserved. Based on the results presented, we propose preliminary molecular maps of the centromere regions of Mus domesticus and Mus spretus. 相似文献
167.
Klaus Fischer Jürgen Kreyling Michaël Beaulieu Ilka Beil Manuela Bog Dries Bonte Stefanie Holm Sabine Knoblauch Dustin Koch Lena Muffler Pierick Mouginot Maria Paulinich J. F. Scheepens Raijana Schiemann Jonas Schmeddes Martin Schnittler Gabriele Uhl Marieke van der Maaten-Theunissen Julia M. Weier Martin Wilmking Robert Weigel Phillip Gienapp 《Heredity》2021,126(1):23
Assessing the genetic adaptive potential of populations and species is essential for better understanding evolutionary processes. However, the expression of genetic variation may depend on environmental conditions, which may speed up or slow down evolutionary responses. Thus, the same selection pressure may lead to different responses. Against this background, we here investigate the effects of thermal stress on genetic variation, mainly under controlled laboratory conditions. We estimated additive genetic variance (VA), narrow-sense heritability (h2) and the coefficient of genetic variation (CVA) under both benign control and stressful thermal conditions. We included six species spanning a diverse range of plant and animal taxa, and a total of 25 morphological and life-history traits. Our results show that (1) thermal stress reduced fitness components, (2) the majority of traits showed significant genetic variation and that (3) thermal stress affected the expression of genetic variation (VA, h2 or CVA) in only one-third of the cases (25 of 75 analyses, mostly in one clonal species). Moreover, the effects were highly species-specific, with genetic variation increasing in 11 and decreasing in 14 cases under stress. Our results hence indicate that thermal stress does not generally affect the expression of genetic variation under laboratory conditions but, nevertheless, increases or decreases genetic variation in specific cases. Consequently, predicting the rate of genetic adaptation might not be generally complicated by environmental variation, but requires a careful case-by-case consideration.Subject terms: Evolutionary genetics, Climate-change ecology, Biodiversity 相似文献
168.
Fluorescence in situ hybridization using simultaneously a combination of DNA probes for the telomeric hexamer repeat (TTAGGG) and the centromerically repeated murine gamma-satellite DNA was applied to analyze the nature of radiation-induced micronuclei in mouse NIH 3T3 fibroblasts. After subtraction of spontaneously occurring micronuclei independent from the dose and time after irradiation, approximately 22% of the radiation-induced micronuclei did not reveal any hybridization signal. Approximately 17% showed one centromeric hybridization signal and about four telomeric signals, suggesting their origin from whole chromosomes. Almost 60% of radiation-induced micronuclei had telomeric signals only, suggesting their origin from acentric fragments. A fraction of micronuclei were found to contain two or more acentric fragments. Micronuclei derived from whole chromosomes or from multiple acentric fragments might, together with DNA synthesis in micronuclei, explain the occurrence of radiation-induced micronuclei with DNA contents greater than the largest chromosome arm. 相似文献
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