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91.
92.
Accumulation of Glucosylceramide and Glucosylsphingosine (Psychosine) in Cerebrum and Cerebellum in Infantile and Juvenile Gaucher Disease 总被引:5,自引:3,他引:2
Abstract: Three major clinical variants of Gaucher disease have been defined: Type I, chronic nonneuronopathic; Type II, acute neuronopathic; and Type III, subacute neuronopathic. In a search for the underlying molecular basis of the neurological manifestations, the concentration and composition of cholesterol, phospholipids, neutral glycosphingolipids, and gangliosides were examined in cerebral and cerebellar cortices of five cases of Type II, eight cases of Type III, and one case of presumed Type I/III. In Type II the concentration of glucosylceramide was 140-530 μmol/kg in cerebral cortex and 51-450 μmol/kg in cerebellar cortex, the highest values found in the most fulminant cases. These concentrations were 20-80 times greater than normal in cerebral cortex and 5-40 times normal in cerebellar cortex. In Type III the concentration of glucosylceramide was 37-65 and 59-1750 μmol/kg in cerebral and cerebellar cortex, respectively. The highest concentrations were found in the cerebellum of patients who had survived splenectomy for several years. The ceramide composition of the accumulated glucosylceramide suggested that brain gangliosides were the major precursors of the glucosylceramide in brains of Type II but in cerebellar cortex in Type III was partly of extracerebral origin. The levels of lactosylceramide and oligohexaosylceramides were slightly raised in all brain specimens from the Gaucher cases. The ganglioside concentration was normal, whereas there was a certain increase in the proportion of GM2 and GM3 gangliosides. The brain glycosphingolipid changes in the Type I/III case were similar but slightly less than those in Type III cases of corresponding age. Glucosylsphingosine (psychosine), never detected in normal human brain, was demonstrated in brains from all the Gaucher cases. The psychosine concentration was highest in Type II cases, 3.8-8.8 and 3.9-12.3 μmol/kg in cerebral and cerebellar cortex, respectively, with the highest values found in the most fulminant cases. In Type III the psychosine concentration varied more widely, 0.8-4.6 and 1.4-6.3 μmol/kg in cerebral and cerebellar cortex, respectively. The lowest value, 0.7 μmol/kg, was found in the Type I/III case. Our method detected psychosine down to 0.01 μmol/kg, which means that the concentration of psychosine was increased at least 100- to 1000-fold in Gaucher grey matter. We suggest that the accumulation of the cell-toxic substance psychosine is the basis for the extensive neuronal cell loss in Gaucher disease, which is most striking in Type II disease. 相似文献
93.
Free Fatty Acids in the Rat Brain in Moderate and Severe Hypoxia 总被引:20,自引:16,他引:4
Mark Gardiner Bengt Nilsson Stig Rehncrona Bo K. Siesjö 《Journal of neurochemistry》1981,36(4):1500-1505
Abstract: The effects of mild, moderate, and severe hypoxia on cerebral cortical concentrations of free fatty acids (FFAs) were investigated in artificially ventilated rats under nitrous oxide anaesthesia. No change occurred during either mild (arterial Po2 35–40 mm Hg) or moderate (Po2 25–30 mm Hg) hypoxia. The effects of severe hypoxia (Po2 about 20 mm Hg) combined with hypotension (mean arterial blood pressure 80–85 mm Hg) varied with the EEG pattern and the tissue energy state. Thus, a major increase in total as well as in individual FFAs occurred first when EEG was severely depressed (almost isoelectric) and energy homeostasis disrupted. On a relative basis the greatest change occurred in free arachidonic acid. It is concluded that hypoxia is associated with an increase in the concentrations of FFAs in brain tissue, provided that tissue oxygen deficiency is severe enough to cause tissue energy failure. However, an increase in FFAs does not invariably accompany minor reductions in the adenylate energy charge (EC) of the tissue. 相似文献
94.
95.
Summary The ultrastructure of the compound eyes of 13 amphipod species has been investigated. An amphipod type of compound eye can be characterized by the constellation and consistency of a number of morphological features, most of which are also found in other compound eyes. The amphipod eye falls into four sub-categories (types). The ampeliscid type has a tripartite aberrant lens eye; the lysianassid type has a reduced or no dioptric apparatus and a hypertrophied rhabdom; the hyperid type possesses a large number of ommatidial units with long crystalline cones and dark instead of reflecting accessory pigment; and finally, the gammarid type can be interpreted as a generalized amphipod type. The lysianassid type is adapted to low light intensities and demonstrates convergent development with the compound eyes of other deep-sea crustaceans. The ampeliscid type is more similar to the gammarid type. The type characterization of the amphipod compound eye might well serve as a basis and incentive for functional studies also revealing adaptational mechanisms.This paper is dedicated to Professor Erik Dahl on his 65th birthday and retirement from the Chair of Structural Zoology, Department of Zoology, University of LundThe investigation has been supported by grants from the Swedish Natural Science Research Council (Grants 2760-009 and 009-43). Our thanks are due to the staffs of the marine biological stations in Espegrend (Norway) and Kristineberg (Sweden) and of the research vessel Jean Charcot, Brest, France. The skilled technical assistance of Mrs. Rita Wallén and Miss Maria Walles is gratefully acknowledged 相似文献
96.
Human corpora lutea of defined ages were excised at operation, cut into pieces and incubated in the presence of HCG, PGF2 alpha and PGE2 alone or in combination. Following incubation cAMP formation in tissue and medium was determined. HCG-stimulated tissue cAMP content was most pronounced at a corpus luteum age of 7-10 days after ovulation. This stimulation was antagonized by PGF2 alpha in corpora lutea older than 6 days. PGE2 stimulated cAMP formation per se and this effect was more pronounced when HCG and PGE2 were combined. A possible role for PGF2 alpha as a luteolytic substance in the human is suggested. 相似文献
97.
Three models for mRNA translation are discussed in the light of available experimental data. It is concluded that the elongation rates vary along a messenger, possibly as a result of a coupling between ribosome movement and mRNA secondary structure. Some promising areas of further experimentation are indicated. 相似文献
98.
Hepatocytes isolated from rat or pig by collagenase perfusion were incubated with [3H]glcyerol and different albumin-bount fatty acids. Among C22 fatty acids docosahexaenoic acid stimulated phosphatidylethanolamine synthesis in rat hepatocytes most effectively. Addition of docosahexaenoic acid plus either palmitic or stearic acid resulted almost in the same stimulation whereas combinations of this acid with lauric or myristic acid had no effect. Lauric acid and myristic acid alone inhibited phosphatidylethanolamine synthesis. The chain length specificity for monoenoic fatty acids was similar, the hexadecenoic and octadecenoic acids (both cis and trans) being most stimulatory. The addition of 0.2 mM ethanolamine markedly stimulated phosphatidylethanolamine synthesis, but most effects of fatty acids were similar in its presence or absence. 相似文献
99.
B A Petersson A Nilsson G St?lenheim 《Journal of immunology (Baltimore, Md. : 1950)》1975,114(5):1581-1584
Hog anaphylatoxin (AT) in concentrations from 0.5 to 5 mug/ml gives a dose-dependent histamine release from human leukocytes. Concentration of 100 mug/ml AT give the same high histamine release as 5 mug/ml. This is in contrast to the histamine release obtained with anti-IgE or allergen, which give low histamine release with high doses. The histamine release obtained with AT is completed in 20 sec and the reaction is temperature- and calcium-dependent. Treatment of cells with AT in the presence or absence of calcium makes them insensitive to another challenge with AT. Such treated cells are fully responsive, however, to challenge with anti-IgE if the pretreatment has been performed in the absence of calcium. This, together with the calcium- and temperature-dependence indicates that the AT-induced histamine release is nontoxic. Treatment of cells with AT in the presence of calcium induces, besides histamine release, decrease in sensitivity to anti-IgE, indicating that both AT and anti-IgE release histamine from the same cells. We discuss to what extent AT and cell-bound Ig share intracellular mechanisms for induction of histamine release. 相似文献
100.
Improving the phenotype predictions of a yeast genome‐scale metabolic model by incorporating enzymatic constraints 下载免费PDF全文
Avlant Nilsson Petri‐Jaan Lahtvee Eduard J Kerkhoven Jens Nielsen 《Molecular systems biology》2017,13(8)
Genome‐scale metabolic models (GEMs) are widely used to calculate metabolic phenotypes. They rely on defining a set of constraints, the most common of which is that the production of metabolites and/or growth are limited by the carbon source uptake rate. However, enzyme abundances and kinetics, which act as limitations on metabolic fluxes, are not taken into account. Here, we present GECKO, a method that enhances a GEM to account for enzymes as part of reactions, thereby ensuring that each metabolic flux does not exceed its maximum capacity, equal to the product of the enzyme's abundance and turnover number. We applied GECKO to a Saccharomyces cerevisiae GEM and demonstrated that the new model could correctly describe phenotypes that the previous model could not, particularly under high enzymatic pressure conditions, such as yeast growing on different carbon sources in excess, coping with stress, or overexpressing a specific pathway. GECKO also allows to directly integrate quantitative proteomics data; by doing so, we significantly reduced flux variability of the model, in over 60% of metabolic reactions. Additionally, the model gives insight into the distribution of enzyme usage between and within metabolic pathways. The developed method and model are expected to increase the use of model‐based design in metabolic engineering. 相似文献