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71.
Summary Using a forward mutation assay we have previously found that N-2-acetylaminofluorene (AAF), a strong chemical carcinogen, induces a majority of frameshift mutations located at specific sequences called mutation hot spots. Among these hot spot sequences, the NarI sequence (GGCGCC), is specific for –2 frameshifts (GGCGCC) GGCC). Interestingly, these frameshift mutations occur independently of a functional umuDC locus. Being interested in elucidating this mutation pathway we have developed a reversion assay that is specific for this class of mutations. The assay is based on the reversion of a +2 frameshift mutant of plasmid pBR322 from tetracycline sensitivity to tetracycline resistance. It is shown that only true reversion events lead to tetracycline resistance. The carcinogen AAF induces this reversion event at a frequency that is increased four- to fivefold over the background frequency. A series of chemical carcinogens which, like AAF, bind covalently to the C8 position of guanine, are compared for their efficiency to induce this specific mutation event. Large variations in the mutagenic efficiency of these chemicals are observed and discussed in terms of the anti/syn conformation of the carcinogen-modified guanine residue. Based on this test, we describe a convenient spot assay that this presently used in our laboratory to isolate Escherichia coli mutants affected in this mutation pathway. 相似文献
72.
Olaf Rieβ Claudia Kammerbauer Lutz Roewer Viktor Steimle Adriane Andreas Ekkehard Albert Tatsuo Nagai Jörg T. Epplen 《Immunogenetics》1990,32(2):110-116
We have investigated the extent of DNA variability in intronic simple (gt)n(ga)m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)n(ga)m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M 34258. 相似文献
73.
74.
A study on the metabolic and hemodynamic actions of hepatic nerve stimulation in the perfused liver of guinea pig and tree shrew as compared to rat was performed, since the density of liver innervation was reported to be different. 1) Nerve stimulation resulted in an increase in glucose release and decrease in lactate uptake or in a shift to output as well as a decrease in portal flow in all three species. The change in glucose output was very similar, that in lactate balance and flow was smaller in tree shrew than in guinea pig and rat. Apparently, the metabolic and hemodynamic changes did not reflect the different densities of liver innervation. 2) The overflow of the neurotransmitter noradrenaline into the hepatic vein differed very clearly in the three animals. In the guinea pig and tree shrew the maximal increase in noradrenaline concentration measured in the effluent was about 6-7-fold higher than in the rat. 3) The content of noradrenaline in the liver in vivo was about five-fold higher in the guinea pig and again another four-fold higher in the tree shrew than in the rat. The contents of adrenaline and dopamine were very low in comparison to those of noradrenaline. The different hepatic noradrenaline contents of the three species investigated are in line with the anatomical findings on the different innervation density. 4) Inhibitors of eicosanoid synthesis reduced the nerve stimulation-dependent metabolic and hemodynamic alterations in guinea pig liver as in rat liver indicating a similar mechanism in these species. Apparently, prostaglandins might be involved as mediators or modulators of nerve actions also in the more densely innervated guinea pig liver and not only in the less densely innervated rat liver.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
75.
Marcelo Hermes-Lima Ana Claudia Tessis Adalberto Vieyra 《Origins of life and evolution of the biosphere》1990,20(1):27-41
In this paper it is shown that the adsorption of 5-adenosine monophosphate (5-AMP) onto precipitated calcium phosphate exhibits a sigmoidal profile as revealed by isotherms at 45 °C. This result indicates a cooperative behavior in the adsorption of 5-AMP. The relationship between adsorption capacity and surface area of the sedimented matrix may be interpreted as an indication that there is a monolayer of the adsorbed nucleotide on the solid surface. The pH dependence of adsorption suggests that the negatively charged phosphoryl group of 5-AMP interacts with a positively charged site (possibly Ca2+) on the matrix surface. The adsorption of the nucleotide is markedly decreased at pH values above 8.0. The Dixon-like plot of the effect of pH suggests an inhibitory role of hydroxyl ions in the adsorption of 5-AMP. At pH 7.5, other anions such as pyrophosphate, tripolyphosphate and carbamyl phosphate also inhibit the adsorption of the nucleotide, probably by interacting with its adsorption site. We suggest that these phosphorylated molecules could have played a role in chemical evolution by modulating the amount of nucleotides adsorbed onto mineral surfaces. The significance of these phenomena in chemical evolution is discussed. 相似文献
76.
77.
TGF-beta and retinoic acid: regulators of growth and modifiers of differentiation in human epidermal cells. 总被引:14,自引:1,他引:13
In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-beta s and retinoic acid (RA) on controlling this balance in normal and malignant human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on keratinocytes. In contrast to retinoids, TGF-beta s acted on mitotically active basal cells to retard cell proliferation. Although withdrawal from the cell cycle is a necessary prerequisite for commitment to terminal differentiation, TGF-beta s inhibited normal keratinization in suprabasal cells and promoted the type of differentiation commonly associated with wound-healing and epidermal hyperproliferation. The actions of TGF-beta s and RA on normal keratinization were synergistic, whereas those on abnormal differentiation associated with hyperproliferation were antagonistic. These observations underscore the notion that environmental changes can act separately on proliferating and differentiating cells within the population. Under the conditions used here, the action of TGF-beta s on human keratinocytes was dominant over RA, and TGF-beta s did not seem to be induced as a consequence of RA treatment. This finding is consistent with the fact that RA accelerated, rather than inhibited, proliferation in raft cultures. Collectively, our data suggest that the effects of both factors on epidermal growth and differentiation are multifaceted and the extent to which their action is coupled in keratinocytes may vary under different conditions and/or in different species. 相似文献
78.
The adsorption of 5′-AMP onto precipitated calcium phosphate (CaPi) requires the presence of soluble calcium and this dependence
exhibits a Michaelian-like behavior. This result suggests that the formation of a complex between 5′-AMP and free Ca2+ (CaAMP) is a prelude to the adsorption of the nucleotide in the solid matrix. At concentrations one order of magnitude higher,
Mn2+ and Mg2+ can substitute for soluble Ca2+ in the adsorption of 5′-AMP onto solid CaPi. However, when added simultaneously with 5′-AMP to a heterogeneous mixture that
contains CaPi and soluble Ca2+, Mn2+ and Mg2+ inhibit the adsorption of 5′-AMP in a concentration-dependent manner. This suggests the formation of complexes that are much
less effective for 5′-AMP adsorption than the CaAMP complex. On the other hand, Mn2+ and Mg2+ cannot promote desorption of the nucleotide attached to the precipitate in the presence of soluble Ca2+ if they are added after adsorption has attained equilibrium. Although desorption of 5′-AMP can be obtained by a sequential
dilution of the soluble phase with buffer and no nucleotide in a process that obeys a Langmuir equation, the lack of effect
of Mn2+ or Mg2+ when adsorption has attained its maximal value suggests strong interactions between the CaAMP complex and the solid matrix
when adsorption equilibrium is reached. The divalent cations present in the matrix also participate with different selectivity
in the attachment of the CaAMP complex, indicating that a cation-exchange mechanism could have acted in the modulation of
adsorptive/desorptive processes involving biomonomers and phosphate surfaces in primitive aqueous environments.
Received: 11 December 1995 / Accepted: 5 April 1996 相似文献
79.
Xp-duplications with and without sex reversal 总被引:5,自引:0,他引:5
Annette Baumstark Gotthold Barbi Mahmoud Djalali Claudia Geerkens Beate Mitulla Torsten Mattfeldt José Carlos Cabral de Almeida Fernando Regla Vargas Juan Clinton Llerena Jr Walther Vogel Walter Just 《Human genetics》1996,97(1):79-86
Duplications in Xp including the DSS (dosage sensitive sex reversal) region cause male to female sex reversal. We investigated two patients from families with Xp duplications. The first case was one of two sisters with karyotype 46,XY, der(22), t(X;22)(p11.3;p11)mat and unambiguous female genitalia. The living sister was developmentally retarded, and showed multiple dysmorphic features and an acrocallosal syndrome. The second case was a boy with a maternally inherited direct duplication of Xp21.3-pter with the breakpoint close to the DSS locus. He had multiple abnormalities and micropenis, but otherwise unambiguous male genitalia. We performed quantitative Southern blot analysis with probes from Xp22.13 to p21.2 to define the duplicated region. Clinical, cytogenetic, and molecular data from both patients were compared with those of previously reported related cases. A comparison of the extragenital symptoms revealed no differences between patients with or without sex reversal. In both cases, the symptoms were non-specific. Among 22 patients with a duplication in Xp, nine had unambiguous female genitalia and a well-documented duplication of the DSS region. Two patients with duplication of DSS showed ambiguous external genitalia. From these data, we conclude that induction of testicular tissue may start in these patients, but that the type of genitalia depends on the degree of subsequent degeneration by a gene in DSS. 相似文献
80.
Claudia Gaspar Iscia Lopes-Cendes Anita L. DeStefano Patrícia Maciel Isabel Silveira Paula Coutinho Patrick MacLeod Jorge Sequeiros Lindsay A. Farrer G. A. Rouleau 《Human genetics》1996,98(5):620-624
Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration originally described in families of Portuguese-Azorean
ancestry. The hypothesis that its present world distribution could result from the spread of an original founder mutation
has been raised. To test this possibility we have conducted a linkage disequilibrium study of markers segregating with the
MJD1 locus in a total of 64 unrelated families of different geographical origins. Significant association was detected between
the MJD1 locus and marker alleles at loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese family, had allele
3 (237 bp) at D14S280. This finding is consistent with a founder effect in our MJD population. However, distinct haplotypes
were observed in patients originating from the two Azorean islands showing the highest disease prevalence; therefore, the
possible existence of more than one founder mutation can not be excluded with the markers currently available.
Received: 27 February 1996 / Revised: 4 June 1996 相似文献