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排序方式: 共有162条查询结果,搜索用时 31 毫秒
1.
Genetic tagging of tumor cells with retrovirus vectors: clonal analysis of tumor growth and metastasis in vivo. 总被引:4,自引:0,他引:4 下载免费PDF全文
B Korczak I B Robson C Lamarche A Bernstein R S Kerbel 《Molecular and cellular biology》1988,8(8):3143-3149
Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a nonmetastatic, aneuploid mouse mammary adenocarcinoma, and SP1HU9L, a metastatic variant of SP1. Cells were infected with delta e delta pMoTN, a replication-defective retrovirus vector which possesses the dominant selectable neo gene and crippled long terminal repeats. G418r colonies were obtained at a frequency of 4 x 10(-3). Southern blot analysis of a number of clones provided evidence of random and heritable integration of one or two copies of the proviral DNA. Clonal evolution of primary tumor growth and the nature of lineage relationships among spontaneous metastases and primary tumors were analyzed by subcutaneously injecting 10(5) cells from a pooled mixture of 3.6 x 10(2) G418r SP1HU9L or 10(4) G418r SP1 colonies into syngeneic CBA/J mice. The most striking finding was the relative clonal homogeneity of advanced primary tumors; they invariably consisted of a small number (less than 10) of distinct clones despite the fact that hundreds or thousands of uniquely marked clones had been injected. In the case of the metastatic SP1HU9L cells, the nature of these "dominant" clones varied from one tumor to another. Analysis of a number of lung metastases revealed that a proportion of them were derived from dominant primary tumor clones and were composed of one, and sometimes two, distinct progenitors. In some animals, all the lung metastases were derived from a common progenitor clone, whereas in others, each metastatic nodule had a different progenitor. The results show the following. (i) Retrovirus vector infection can be used to introduce large numbers of unique and stable clonal markers into tumor cell populations. (ii) The progeny of a very limited number of clones dominate in advanced primary tumors. (iii) Mammary carcinoma metastases are of mono- or biclonal origin. The significance of the results is discussed. 相似文献
2.
Rajender K. Kamboj Darryle D. Schoepp Stephen Nutt Lee Shekter Bozena Korczak Rebecca A. True Vikarna Rampersad Dennis M. Zimmerman Michael A. Wosnick 《Journal of neurochemistry》1994,62(1):1-9
Abstract: Kainate is a potent neuroexcitatory agent; its neurotoxicity is thought to be mediated by an ionotropic receptor with a nanomolar affinity for kainate. In this report, we describe the cloning of a cDNA encoding a human glutamate ionotropic receptor subunit protein from a human hippocampal library. This cDNA, termed humEAA1, is most closely related to rat and human cDNAs for kainate receptor proteins and, when expressed in COS or Chinese hamster ovary cells, is associated with high-affinity kainate receptor binding. We have successfully established cell lines stably expressing humEAA1. This is the first report of establishment of stable cell lines expressing a glutamate receptor subunit. The relative potency of compounds for displacing [3 H] kainate binding of humEAA1 receptors expressed in these stable cell lines was kainate > quisqualate > domoate > L-glutamate > ( RS )-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid > dihydro-kainate > 6, 7-dinitroquinoxaline-2, 3-dione > 6-cyano-7-nitroquinoxaline-2, 3-dione. Homooligomeric expression of humEAA1 does not appear to elicit ligand-gated ion channel activity. Nevertheless, the molecular structure and pharmacological characterization of high-affinity kainate binding of the humEAA1 expressed in the stable cell line (ppEAA1–16) suggest that the humEAA1 is a subunit protein of a human kainate receptor complex. 相似文献
3.
The ATP-binding-cassette transmembrane transporters (ABC transporters)
known from vertebrates belong to four major subfamilies: (1) the P-
glycoproteins (Pgp); (2) the cystic fibrosis transmembrane conductance
regulators (CFTR); (3) the Tap proteins encoded with the major
histocompatibility complex of mammals; and (4) the peroxisomal membrane
proteins. Both Pgp and CFTR have a structure suggesting a past internal
gene duplication; a phylogenetic analysis indicated that these duplications
occurred independently, while an independent tandem gene duplication
occurred in the case of the Tap family. Both the Pgp and Tap proteins show
evidence of relationship to bacterial ABC transporters lacking internal
duplication, and both are significantly more closely related to the HlyB
and MsbA families of transporters from purple bacteria than they are to ABC
transporters from nonpurple bacteria. The simplest hypothesis to explain
this observation is that eukaryotic Pgp and Tap genes are descended from a
mitochondrial gene or genes that were subsequently translocated to the
nuclear genome. The Pgp genes of eukaryotes are characterized by a
remarkable degree of convergent evolution between the ATP-binding cassettes
of their N- terminal and C-terminal halves, whereas no such convergence is
seen between the two halves of CFTR genes or between the duplicated Tap
genes. Exon 13 of the CFTR gene, which encodes a putative regulatory domain
not found in other ABC transporters apart from CFTR, showed high levels of
both synonymous and nonsynonymous difference in comparisons among different
mammalian species, suggesting that this region is a mutational hot spot.
相似文献
4.
5.
X Xiao G Hintermann AL Demanin J Piret 《Journal of industrial microbiology & biotechnology》1996,16(4):261-262
Streptomyces glaucescens is shown to possess -lactamase activity which is inhibitable by clavulanate. This is important in regard to its use as a cloning host for enzymes of \-lactam biosynthesis. 相似文献
6.
ERIC S. BONO PATRICK SMOLINSKI AL CASAGRANDA JUNDE XU 《Computer methods in biomechanics and biomedical engineering》2013,16(2):125-131
The Shear-slip Mesh Update Method (SSMUM) is being used in flow simulations involving large but regular displacements of one or more boundaries of the computational domain. We follow up the earlier discussion of the method with notes on practical implementation aspects. In order to establish a benchmark problem for this class of flow problems, we define and report results from a two-dimensional viscous flow around a rotating stirrer in a square chamber. The application potential of the method is demonstrated in the context of biomedical design problem, as we perform an analysis of blood flow in a centrifugal left ventricular assist device, or blood pump, which involves a rotating impeller in a non-axisymmetric housing. 相似文献
7.
8.
HENRY SILVERMAN BABIKER AHMED SAMAR AJEILET SUMAIA AL‐FADIL SUHAIL AL‐AMAD HADIR EL‐DESSOUKY IBRAHIM EL‐GENDY MOHAMED EL‐GUINDI MUSTAFA EL‐NIMEIRI RANA MUZAFFAR AZZA SALEH 《Developing world bioethics》2010,10(2):70-77
To help ensure the ethical conduct of research, many have recommended educational efforts in research ethics to investigators and members of research ethics committees (RECs). One type of education activity involves multi‐day workshops in research ethics. To be effective, such workshops should contain the appropriate content and teaching techniques geared towards the learning styles of the targeted audiences. To ensure consistency in content and quality, we describe the development of a curriculum guide, core competencies and associated learning objectives and activities to help educators organize research ethics workshops in their respective institutions. The curriculum guide is divided into modular units to enable planners to develop workshops of different lengths and choose content materials that match the needs, abilities, and prior experiences of the target audiences. The content material in the curriculum guide is relevant for audiences in the Middle East, because individuals from the Middle East who participated in a Certificate Program in research ethics selected and developed the training materials (e.g., articles, powerpoint slides, case studies, protocols). Also, many of the activities incorporate active‐learning methods, consisting of group work activities analyzing case studies and reviewing protocols. The development of such a workshop training curriculum guide represents a sustainable educational resource to enhance research ethics capacity in the Middle East. 相似文献
9.
Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1 总被引:8,自引:1,他引:7
There are 10 gene families that have members on both human chromosome 6
(6p21.3, the location of the human major histocompatibility complex [MHC])
and human chromosome 9 (mostly 9q33-34). Six of these families also have
members on mouse chromosome 17 (the mouse MHC chromosome) and mouse
chromosome 2. In addition, four of these families have members on human
chromosome 1 (1q21-25 and 1p13), and two of these have members on mouse
chromosome 1. One hypothesis to explain these patterns is that members of
the 10 gene families of human chromosomes 6 and 9 were duplicated
simultaneously as a result of polyploidization or duplication of a
chromosome segment ("block duplication"). A subsequent block duplication
has been proposed to account for the presence of representatives of four of
these families on human chromosome 1. Phylogenetic analyses of the 9 gene
families for which data were available decisively rejected the hypothesis
of block duplication as an overall explanation of these patterns. Three to
five of the genes on human chromosomes 6 and 9 probably duplicated
simultaneously early in vertebrate history, prior to the divergence of
jawed and jawless vertebrates, and shortly after that, all four of the
genes on chromosomes 1 and 9 probably duplicated as a block. However, the
other genes duplicated at different times scattered over at least 1.6
billion years. Since the occurrence of these clusters of related genes
cannot be explained by block duplication, one alternative explanation is
that they cluster together because of shared functional characteristics
relating to expression patterns.
相似文献
10.
Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies 总被引:13,自引:8,他引:5
Estimation of evolutionary distances from coding sequences must take into
account protein-level selection to avoid relative underestimation of longer
evolutionary distances. Current modeling of selection via site-to-site rate
heterogeneity generally neglects another aspect of selection, namely
position-specific amino acid frequencies. These frequencies determine the
maximum dissimilarity expected for highly diverged but functionally and
structurally conserved sequences, and hence are crucial for estimating long
distances. We introduce a codon- level model of coding sequence evolution
in which position-specific amino acid frequencies are free parameters. In
our implementation, these are estimated from an alignment using methods
described previously. We use simulations to demonstrate the importance and
feasibility of modeling such behavior; our model produces linear distance
estimates over a wide range of distances, while several alternative models
underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and
first/second/third-codon-position differences, arise as a natural
consequence of the site-to-site differences in amino acid frequencies.
相似文献