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121.
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Summary Previous attempts to produce nonenzymatic template-directed oligomerizations of activated pyrimidines on polypurine templates have been unsuccessful. The only efficient reactions are those where the template is composed primarily of pyrimidines, especially cytosine. Because molecular evolution requires that a synthesized daughter polynucleotide be capable of acting as a template for the synthesis of the original polynucleotide, the one-way replication achieved thus far is inadequate to initiate an evolving system.Several uracil analogs were used in this investigation in order to search for possible replacements for uracil. The monomers used in this investigation were the imidazolides of UMP, xanthosine 5-monophosphate, the bis-monophosphates of the acyclic nucleosides of uracil, and 2,4-quinazolinedione. The concentrations of various salts, buffers, pH, and temperature were among the different variables investigated in attempts to find conditions that would permit template-directed oligomerizations. Although the different monomers in this study demonstrated varying abilities to form very short oligomers, we were unable to detect any enhancement of this oligomerization that could be attributed to the poly(A) template.Although special conditions might be found that would allow purine-rich templates to work, these reactions cannot be considered robust. The results of our experiments suggest that pyrimidines were not part of the original replicating system on the primitive Earth. It has already been shown that ribose is an unlikely component of the first replicating systems, and we now suggest that phosphate was absent as well. This is due to the low solubility of phosphate in the present ocean (3×10–6 M), as well as the difficulty of prebiotic activation of phosphates. 相似文献
124.
A. M. Schor A. E. Canfield P. Sloan S. L. Schor 《In vitro cellular & developmental biology. Animal》1991,27(8):651-659
Summary We have previously reported that pericytes derived from retinal and brain microvessels aggregate into nodules soon after reaching
confluence. Nodule formation involves a reorganization of the cells resulting in the presence of sparse cells, confluent monolayers,
multilayers, sprouts, and nodules within the same culture dish. Extracellular calcification occurs only within the nodules,
demonstrating that pericytes are capable of undergoing osteogenic differentiation in culture and that this differentiation
is related to nodule formation. Using immunofluorescence we have now studied the distribution of laminin, type IV collagen,
type X collagen, and tenascin in pericyte cultures during nodule formation. These matrix macromolecules were also identified
by a combination of biochemical techniques, including Northern blot hybridization, immunoblotting and sodium dodecyl sulfate-polyacrylamide
gel electrophoresis. A molecule that seems to be related to type X collagen was demonstrated by the presence of a pepsin-resistant,
collagenase-sensitive polypeptide of molecular weight approximately 45 kDa. The production of laminin, type X-related collagen,
and tenascin by pericytes has not been previously reported. Our results suggest that the synthesis or distribution or both
of these molecules is dependent on the state of pericyte differentiation. The expression of laminin, type IV collagen, and
type X-related collagen was maximal in multilayer areas, sprouts, and nodules. Tenascin appeared homogeneously distributed
in monolayer and multilayer areas; when calcified nodules were present, the anti-tenascin serum preferentially decorated a
discrete area circumscribing the nodules. Tenascin and type X collagen have been found transiently in vivo preceding calcification;
their possible role in this process is not known. Our results also suggest an association between laminin, type IV collagen,
and calcification. The in vitro experimental system described here may help to clarify the role of matrix macromolecules in
the calcification process. 相似文献
125.
The only species of fission yeasts capable of growing on glycerol or dihydroxyacetone were Schizosaccharomyces pombe and S. malidevorans. When growing on glycerol or grown on glucose until it was exhausted, these species contained glycerol:NAD+ 2-oxidoreductase and dihydroxyacetone kinase but no glycerol kinase, consistent with utilization of glycerol via dihydroxyacetone. When grown to exhaustion of glucose, S. octosporus, S. slooffiae and S. japonicus contained dihydroxyacetone kinase but no glycerol:NAD+ 2-oxidoreductase or glycerol kinase. Prior to exhaustion of glucose in the medium, all species contained dihydroxyacetone kinase, all species except S. japonicus contained glycerol:NADP+ 2-oxidoreductase, and only S. pombe and S. malidevorans contained glycerol:NAD+ 2-oxidoreductase. Possible roles for the glycerol:NAD+ 2-oxidoreductase, glycerol:NADP+ 2-oxidoreductase and dihydroxyacetone kinase in metabolism of glycerol and dihydroxyacetone are discussed.Non-standard abbreviations DHA
dihydroxyacetone
- DHAK
dihydroxyacetone kinase
- DHAP
dihydroxyacetone phosphate
- GK
glycerol kinase
- G2DH-NAD
glycerol
- NAD+
2-oxidoreductase
- G2DH-NADP
glycerol
- NADP+
2-oxidoreductase
- MEA
malt extract agar
- YEP
yeast extract phosphate medium 相似文献
126.
Glycerol:NADP+ 2-oxidoreductase (EC 1.1.1.156) was isolated from Schizosaccharomyces pombe, purified and characterized. It had an Mr of 57,000, and SDS-PAGE revealed two polypeptides, of Mr 25,000 and 30,000. Its coenzyme requirement was satisfied exclusively by NADP. The pH optimum for glycerol oxidation was 9.5, for dihydroxyacetone reduction 6.0. Rates of oxidation with some structurally related diols were three- to six-fold lower than for glycerol, while glyceraldehyde and other carbonyl compounds showed negligible rates of reduction. Neither monovalent nor divalent cations activated the enzyme. Apparent Km and Vmax values were determined. The enzyme is similar to glycerol dehydrogenases isolated from Mucor javanicus and from Dunaliella parva but differs considerably from the glycerol:NAD+ 2-oxidoreductase of S. pombe. 相似文献
127.
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129.
Evanthia Galanis Stephen Frytak Kendrith M. Rowland Jr. Jeff A. Sloan Vanda A. Lennon 《Cancer immunology, immunotherapy : CII》1999,48(2-3):85-90
The aims of this study were to investigate, in patients with newly diagnosed small-cell lung carcinoma (SCLC), whether or
not there may be a relationship between the presence, type or titer of circulating neuronal autoantibodies and (i) the extent
of SCLC dissemination at presentation, (ii) the development of peripheral neuropathy during platinum chemotherapy, (iii) survival
time. We studied stored serum from 58 patients with uncomplicated SCLC who had participated in two trials conducted by the
North Central Cancer Treatment Group (NCCTG); 29 had extensive disease and 29 had limited disease. No patient had neuropathy
or other neurological or paraneoplastic problems at the time of enrollment but each group included 14 or 15 patients respectively
who developed peripheral neuropathy in the course of chemotherapy. We tested five consecutive serum specimens from each patient
in blinded fashion by (i) an indirect immunofluorescence assay optimized to detect neuron-restricted nuclear and cytoplasmic
antibodies (triple substrate of mouse cerebellum, gut and kidney), and (ii) immunoprecipitation assays to detect neuronal
Ca2+-channel-binding antibodies (N-type and P/Q-type). Sera that were positive by immunofluorescence were analyzed further by
Western blotting. Neuronal autoantibodies were significantly more frequent in patients who had limited SCLC at presentation
(12/29 or 41% positive) than in those with extensive SCLC (5/29 or 17% positive, P = 0.02). Neuronal autoantibodies of nuclear or cytoplasmic specificity were found in 50% of the seropositive patients with
limited SCLC (21% of the total group), but in no patient with extensive SCLC (P = 0.01). The frequency of neuronal autoantibodies did not differ significantly among patients who did and did not develop
peripheral neuropathy. Titers fell progressively during chemotherapy and did not rise again when peripheral neuropathy became
clinically evident. This argues against a synergism between drug toxicity and neuronal autoimmunity as the mechanism of platinum-associated
peripheral neuropathy. Seropositivity for neuronal autoantibodies did not affect the survival of patients with either limited
or extensive SCLC. It is conceivable that the immunosuppression attendant on combined cisplatin/etoposide therapy cancels
a pre-existing protective antitumor immune response (presumably cytotoxic-T-cell-mediated) for which the nuclear and cytoplasmic
paraneoplastic IgG autoantibodies serve as a surrogate marker. Testing of this hypothesis would require the survival of seropositive
and seronegative patients to be compared in a larger trial, using a therapeutic modality that does not compromise immunocompetence.
Received: 20 November 1998 / Accepted: 6 January 1999 相似文献
130.