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91.
Nichols DH Pauley S Jahan I Beisel KW Millen KJ Fritzsch B 《Cell and tissue research》2008,334(3):339-358
At embryonic day 8.5, the LIM-homeodomain factor Lmx1a is expressed throughout the otic placode but becomes developmentally restricted to non-sensory epithelia of the ear (endolymphatic
duct, ductus reuniens, cochlea lateral wall). We confirm here that the ears of newborn dreher (Lmx1a
dr) mutants are dysmorphic. Hair cell markers such as Atoh1 and Myo7 reveal, for the first time, that newborn Lmx1a mutants have only three sensory epithelia: two enlarged canal cristae and one fused epithelium comprising an amalgamation
of the cochlea, saccule, and utricle (a “cochlear-gravistatic” endorgan). The enlarged anterior canal crista develops by fusion
of horizontal and anterior crista, whereas the posterior crista fuses with an enlarged papilla neglecta that may extend into
the cochlear lateral wall. In the fused endorgan, the cochlear region is distinguished from the vestibular region by markers
such as Gata3, the presence of a tectorial membrane, and cochlea-specific innervation. The cochlea-like apex displays minor disorganization
of the hair and supporting cells. This contrasts with the basal half of the cochlear region, which shows a vestibular epithelium-like
organization of hair cells and supporting cells. The dismorphic features of the cochlea are also reflected in altered gene
expression patterns. Fgf8 expression expands from inner hair cells in the apex to most hair cells in the base. Two supporting cell marker proteins,
Sox2 and Prox1, also differ in their cellular distribution between the base and the apex. Sox2 expression expands in mutant canal cristae prior to their enlargement and fusion and displays a more diffuse and widespread
expression in the base of the cochlear region, whereas Prox1 is not detected in the base. These changes in Sox2 and Prox1 expression suggest that Lmx1a expression restricts and sharpens Sox2 expression, thereby defining non-sensory and sensory epithelium. The adult Lmx1a mutant organ of Corti shows a loss of cochlear hair cells, suggesting that the long-term maintenance of hair cells is also
disrupted in these mutants.
This work was supported by grants from the NCRR/COBRE (P20 RR 018788; D.H.N.) and NIH (RO1 DC 005590; B.F.). Parts of this
investigation were conducted in a facility constructed with support of a Research Facilities Improvement Program Grant from
the National Center for Research Resources, National Institutes of Health. We acknowledge the use of the confocal microscope
facility of the NCCB, supported by EPSCoR EPS-0346476 (CFD 47.076), and of the University of Nebraska microarray facility,
supported by NCRR/COBRE. 相似文献
92.
Proprioceptor pathway development is dependent on Math1 总被引:12,自引:0,他引:12
Bermingham NA Hassan BA Wang VY Fernandez M Banfi S Bellen HJ Fritzsch B Zoghbi HY 《Neuron》2001,30(2):411-422
93.
94.
Wilson SM Householder DB Coppola V Tessarollo L Fritzsch B Lee EC Goss D Carlson GA Copeland NG Jenkins NA 《Genomics》2001,74(2):228-233
Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the v(J) allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foramen,the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss. 相似文献
95.
In the photosynthetic reaction centre (RC) from the purple bacterium Rhodobacter sphaeroides, the primary quinone, a ubiquinone-10 (Q(A)), has been substituted by anthraquinone. Three-dimensional crystals have been grown from the modified RC and its structure has been determined by X-ray crystallography to 2.4 A resolution. The bindings of the head-group from ubiquinone-10 and of the anthraquinone ring are very similar. In particular, both rings are parallel to each other and the hydrogen bonds connecting the native ubiquinone-10 molecule to AlaM260 and HisM219 are conserved in the anthraquinone containing RC. The space of the phytyl tail missing in the anthraquinone exchanged RC is occupied by the alkyl chain of a detergent molecule. Other structural changes of the Q(A)-binding site are within the limit of resolution. Our structural data bring strong credit to the very large amount of spectroscopic data previously achieved in anthraquinone-replaced RCs and which have participated in the determination of the energetics of the quinone system in bacterial RCs. 相似文献
96.
97.
Günter Fritzsch 《Radiation and environmental biophysics》1970,7(1):33-39
Zusammenfassung Stabilitätsuntersuchungen mit Hilfe der Thermodynamik irreversibler Prozesse und offener Systeme gestatten, verschiedene typische Zellprozesse physikalisch zu beschreiben. In dieser Arbeit wird anhand eines einfachen Modells der äueren Zellmembran versucht, das Wachstum von Einzelzellen in Abhängigkeit von der Konzentration des umgebenden Nährmediums thermodynamisch zu begründen. Systeme, die sich nur von einer Substanz ernähren, nehmen bei geringer Konzentration dieser Substanz (Hunger) stabile stationäre Zustände ein (kein Wachstum), bei höherer Konzentration wird dieser Zustand instabil (Wachstum). Im Falle mehrerer Nahrungssubstanzen nimmt das System auch dann stabile stationäre Zustände ein (kein Wachstum), wenn bei sonst ausreichender Nahrung nur eine Nahrungskomponente fehlt bzw. in zu geringer Menge vorhanden ist. Um Wachstum zu ermöglichen, müssen alle Nahrungskomponenten in gewissen Mindestkonzentrationen vorhanden sein.
Herrn Prof. Dr. W. Beier und Herrn Dr. rer. nat. habil. F. Pliquett danke ich für die intensive Unterstützung dieser Arbeit. 相似文献
On the investigation of the growth of single cells by means of thermodynamics of irreversible processes and open systems
Summary Several typical cell processes can be described by means of stability investigations of irreversible thermodynamics. This paper is an attempt to base the cell growth thermodynamically in dependence on the concentration of the surrounding food by using a simple model of the outer cell membrane. A stationary state of a system, feeding only on one substance, is stable, if the concentration of the substance is sufficiently low (starving cell — no growth); at higher concentrations this state can become an unstable one (growth). In the case the cell is feeding on many substances its stationary states are also stable (no growth), if only one component is absent or shows a sufficiently low concentration even at high concentrations of all the other substances. To launch growth all necessary food components must show a certain minimum concentration depending on the other concentrations.
Herrn Prof. Dr. W. Beier und Herrn Dr. rer. nat. habil. F. Pliquett danke ich für die intensive Unterstützung dieser Arbeit. 相似文献
98.
A Plastic Embedding Technique for Analyzing Fluorescent Dextran-Amine Labelled Neuronal Profiles 总被引:1,自引:0,他引:1
A plastic embedding technique employing fluorescently labelled dextran-amines is described. After application of tracer to cut nerves and appropriate transport time, animals were fixed in paraformaldehyde. Subsequently their brains were dissected, heads and brains were dehydrated, embedded in methacrylate and sectioned serially on a rotary microtome. Plastic sections allow high resolution of single neuron profiles and complete serial reconstruction of un-distorted sections, including embryos with large amounts of yolk. In conjunction with whole mount analysis and double labelling, this technique can accurately reveal the spatial relationships of nerve components throughout development. 相似文献
99.
In order to produce monoclonal antibodies directed against different epitopes of the neurohypophyseal hormone vasopressin, the hormone was coupled to carrier proteins via photoreactive groups at different positions in the vasopressin sequence: [2-(4-azidophenylalanine), 8-arginine]vasopressin (peptide P1, photoreactive group at position 2) and desamino-[8-N6-(4-azidophenylamidino)lysine]vasopressin (peptide P2, photoreactive group at position 8) were conjugated to thyroglobulin by flash photolysis. Monoclonal antibodies against these conjugates bound ([3H]8-arginine]vasopressin with dissociation constants ranging over 40-400 nM. Epitope analysis by means of competitive ELISA showed that the monoclonal antibody obtained with peptide P1 as hapten was directed against the C-terminal acyclic tripeptide when its conformation was stabilized by interaction with the disulphide-linked cyclic hexapeptide. In contrast, the epitope analysis of three monoclonal anti-(peptide P2) antibodies demonstrated that they recognized antigenic determinants in the cyclic hexapeptide ring, mainly the hydrophobic surface formed by Tyr2 and Phe3. Our results suggest that monoclonal antibodies against different epitopes in small peptide hormones can be generated selectively by using photoreactive peptides in such a way that different antigenic sites are exposed in the hapten-carrier conjugate. 相似文献
100.
The ATP analog 6-[(3-carboxy-4-nitrophenyl)thiol]-9-beta-D-ribofuranosylpurine 5'-triphosphate (Nbs6ITP) is slowly hydrolyzed at pH 7.4 by the (Na+ + K+)-ATPase, whereas it binds covalently at pH 8.5 and inhibits the enzyme irreversibly. Time courses of irreversible inhibition could only be fitted to a model in which the enzyme can exist in two slowly interchangeable states, one of which is enzymatically active and binds Nbs6ITP first reversibly and then covalently. Arguments that the covalent binding occurs at a low affinity nucleotide binding site are: (a) similarity of the Ki Nbs6ITP for the reversible and the irreversible inhibition and of K0.5 for ATP protection; (b) stoichiometry of covalent Nbs6ITP binding per alpha subunit of 0.8; and (c) change of complex substrate dependence of the enzyme to a Michaelis-Menten type after Nbs6ITP modification. This change in kinetics and the finding that the Nbs6ITP inactivation at a low affinity nucleotide binding site is increased by micromolar ADP concentrations indicates that the (Na+ + K+)-ATPase contains two different nucleotide binding sites. Since studies of nucleotide effects on enzyme inactivation by 5,5'-dithiobis(2-nitrobenzoic acid) did not confirm the hypothesis of an SH-group in a nucleotide binding site, Nbs6ITP may bind to another functional group, e.g. to an OH-group of tyrosine. 相似文献