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31.
A highly polymorphic locus cloned from the breakpoint of a chromosome 11p13 deletion associated with the WAGR syndrome 总被引:2,自引:0,他引:2
Tom Glaser D. J. Driscoll Stylianos Antonarakis David Valle David Housman 《Genomics》1989,5(4):880-893
Children with constitutional deletions of chromosome 11p13 suffer from aniridia, genitourinary malformations, and mental retardation and are predisposed to develop bilateral Wilms tumor (the WAGR syndrome). The critical region for these defects has been narrowed to a segment of band 11p13 between the catalase and the beta-follicle-stimulating hormone genes. In this report, we have cloned the endpoints from a WAGR patient whose large cytogenetic deletion, del(11)(p14.3::p13), does not include the catalase gene. The deletion was characterized using DNA polymorphisms and found to originate in the paternally derived chromosome 11. The distal endpoint was identified as a rearrangement of locus D11S21 in conventional Southern blots of the patient's genomic DNA, but was not detected in leukocyte DNA from either parent or in sperm DNA from the father. The proximal endpoint was isolated by cloning the junction fragment and was mapped in relation to other markers and breakpoints. It defines a new locus in 11p13-delta J, which is close to the Wilms tumor gene and the breakpoint cluster region (TCL2) of the frequent t(11;14)(p13;q11) translocation in acute T-cell leukemia. An unusual concentration of base pair substitutions was discovered at delta J, in which 9 of 44 restriction sites tested (greater than 20%) vary in the population. This property makes delta J one of the most polymorphic loci on chromosome 11 and may reflect an underlying instability that contributed to the original mutation. The breakpoint extends the genetic map of this region and provides a useful marker for linkage studies and the analysis of allelic segregation in tumor cells. 相似文献
32.
G M Clore P C Driscoll P T Wingfield A M Gronenborn 《Journal of molecular biology》1990,214(4):811-817
A low resolution solution structure of the cytokine interleukin-1 beta, a 153 residue protein of molecular weight 17,400, has been determined on the basis of 446 nuclear Overhauser effect (NOE) derived approximate interproton distance restraints involving solely NH, C alpha H and C beta H protons, supplemented by 90 distance restraints for 45 hydrogen bonds, and 79 phi torsion angle restraints. With the exception of 27 C alpha H-C alpha H NOEs, all the NOEs were assigned from a three-dimensional 1H-1H NOE 15N-1H heteronuclear multiple quantum coherence (HMQC) spectrum. The torsion angle restraints were obtained from accurate 3JHN alpha coupling constants measured from a HMQC-J spectrum, while the hydrogen bonds were derived from a qualitative analysis of the NOE, coupling constant and amide exchange data. A total of 20 simulated annealing (SA) structures was computed using the hybrid distance geometry-dynamical simulated annealing method. The solution structure of IL-1 beta comprises 12 beta-strands arranged in three pseudo-symmetrical topological units (each consisting of 5 anti-parallel beta-strands), joined by turns, short loops and long loops. The core of the structure, which is made up of the 12 beta-strands, together with the turns joining strands I and II, strands VIII and IX and strands X and XI, is well determined with a backbone atomic root-mean-square (r.m.s.) distribution about the mean co-ordinate positions of 1.2(+/- 0.1) A. The loop conformations, on the other hand, are poorly determined by the current data. A comparison of the core of the low resolution solution structure of IL-1 beta with that of the X-ray structure indicates that they are similar, with a backbone atomic r.m.s. difference of only 1.5 A between the co-ordinates of the restrained minimized mean of the SA structures and the X-ray structure. 相似文献
33.
We have investigated the development of Ca2+-dependent gamma-[3H]aminobutyric acid [( 3H]GABA) release in superfused growth cone fractions isolated from rats between the postnatal ages of 1 and 11 days. We have compared this release with the overall morphology of the subcellular fractions, and identified those structures taking up [3H]GABA by electron microscopical autoradiography. In fractions isolated from rats between 1 and 5 days, K+-evoked [3H]GABA release was completely independent of extracellular Ca2+. After 5 days a Ca2+ dependency appeared, which increased with age, such that by 10 days approximately 50% of the K+-evoked release was Ca2+ dependent. Electron microscopical analysis showed that, at all ages, large numbers of GABAergic growth cones were present in the subcellular fractions. Up to postnatal day 5, the growth cones were synaptic vesicle sparse but, after this age, increasing numbers of synaptic vesicle-containing growth cones were seen. These results suggest that during maturation of GABAergic growth cones into synapses there is, initially, a mechanism for release that is independent of extracellular Ca2+ and that the appearance of a Ca2+-dependent [3H]GABA release from growth cones correlates with the appearance of synaptic vesicles. 相似文献
34.
A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. 总被引:38,自引:12,他引:26 下载免费PDF全文
DiGeorge syndrome (DGS), a developmental field defect of the third and fourth pharyngeal pouches, is characterized by aplasia or hypoplasia of the thymus and parathyroid glands and by conotruncal cardiac malformations. Cytogenetic studies support the presence of a DGS critical region in band 22q11. In the present study, we report the results of clinical, cytogenetic, and molecular studies of 14 patients with DGS. Chromosome analysis, utilizing high-resolution banding techniques, detected interstitial deletions in five probands and was inconclusive for a deletion in three probands. The remaining six patients had normal karyotypes. In contrast, molecular analysis detected DNA deletions in all 14 probands. Two of 10 loci tested, D22S75 and D22S259, are deleted in all 14 patients. A third locus, D22S66, is deleted in the eight DGS probands tested. Physical mapping using somatic cell hybrids places D22S66 between D22S75 and D22S259, suggesting that it should be deleted in the remaining six cases. Parent-of-origin studies were performed in five families. Four probands failed to inherit a maternal allele, and one failed to inherit a paternal allele. On the basis of these families, and of six maternally and five paternally derived unbalanced-translocation DGS probands in the literature, parent of origin or imprinting does not appear to play an important role in the pathogenesis of DGS. Deletion of the same three loci in all 14 DGS probands begins to delineate the region of chromosome 22 critical for DGS and confirms the hypothesis that submicroscopic deletions of 22q11 are etiologic in the vast majority of cases. 相似文献
35.
Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis. 总被引:4,自引:2,他引:2 下载免费PDF全文
36.
Joanne McLaurin Geralyn C. Trudel Ivan T. Shaw Jack P. Antel Neil R. Cashman 《Developmental neurobiology》1995,26(2):283-293
We have developed a series of immortal human-human hybrid cell lines that express phenotypic characteristics of primary oligodendrocytes, by fusing a 6-thioguanine–resistant mutant of the human rhabdomyosarcoma RD with adult human oligodendrocytes by a lectin-enhanced polyethylene glycol procedure. Hybrids were selected in an aminopterin-containing media. In contrast to the tumor parent cells, a hybrid clone M03.13 expressed surface immunoreactivity for galactosyl cerebroside and intracellular immunoreactivity for myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). Serum deprivation or chronic treatment with a protein kinase C activator 4-β-phorbol 12-myristate 13-acetate (PMA), but not dibutyl cyclic adenosine monophosphate induced coordinate up-regulation or de novo induction of oligodendrocyte phenotypic markers with concomitant down-regulation of GFAP expression. Consistent with immunohistochemical studies, northern blot analysis demonstrated that both MBP and PLP mRNA were up-regulated in MO3.13 cells by PMA treatment. M03.13 cells provide an immortalized clonal model system suitable for study of gene expression subserving oligodendrocyte and astrocyte phenotypes. © 1995 John Wiley & Sons, Inc. 相似文献
37.
Bloom Syndrome and Maternal Uniparental Disomy for Chromosome 15 总被引:4,自引:1,他引:3
Trevor Woodage Madhuri Prasad Joanne W. Dixon Roslyn E. Selby Dennis R. Romain Letizia M. Columbano-Green David Graham Peter K. Rogan James R. Seip Arabella Smith Ronald J. Trent 《American journal of human genetics》1994,55(1):74-80
Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 相似文献
38.
Joanne Mcandrew Philip S. Rudland Angela M. Platt-Higgins John A. Smith 《The Histochemical journal》1994,26(4):355-366
Summary Immunoreactive alpha-transforming growth factor (-TGF) was shown by immunocytochemistry to be present in the rat mammary gland at various stages of development, the staining being most intense in mature myoepithelial cells. -TGF was also detected in the secretions of the mammary glands of pregnant and lactating rats. -TGF in the extracts of rat mammary glands at each stage of development, and in several rat mammary cell lines and in culture medium in which they had been grown, was shown by Western blotting to consist primarily of a protein of molecular weight 50 kDa. The amount of this protein was greater in the mammary gland of the lactating rat than in resting or involuting glands. -TGF was also found in some, but not all, human breast carcinomas, and in benign hyperplastic breast diseases. 相似文献
39.
Influence of nitrate on uptake of ammonium by nitrogen-depleted soybean: is the effect located in roots or shoots? 总被引:4,自引:1,他引:3
Saravitz Carole H.; Chaillou Sylvain; Musset Joanne; Raper C. David Jr.; Morot-Gaudry Jean-Francis 《Journal of experimental botany》1994,45(11):1575-1584
In non-nodulated soybean [Glycine max (L.) Merrill cv. Ransom]plants that were subjected to 15 d of nitrogen deprivation inflowing hydroponic culture, concentrations of nitrogen declinedto 1.0 and 1.4mmol Ng1 dry weight in shoots and roots,respectively, and the concentration of soluble amino acids (determinedas primary amines) declined to 40µmol g1 dry weightin both shoots and roots. In one experiment, nitrogen was resuppliedfor 10 d to one set of nitrogen-depleted plants as 1.0 mol m3NH4+ to the whole root system, to a second set as 0.5 mol m3NH4+ plus 0.5 mol m3 NO3 to the whole root system,and to a third set as 1.0 mol m3 NH4+ to one-half ofa split-root system and 1.0 mol m3 NO3 to theother half. In a second experiment, 1.0 mol m3 of nitrogenwas resupplied for 4 d to whole root systems in NH4+ : NO3ratios of 1:0, 9:1, and 1:1. Nutrient solutions were maintainedat pH 6.0. When NH4+ was resupplied in combination with NO3 to thewhole root system in Experiment I, cumulative uptake of NH4+for the 10 d of resupply was about twice as great as when NH4+was resupplied alone. Also, about twice as much NH4+ as NO3was taken up when both ions were resupplied to the whole rootsystem. When NH4+ and NO3 were resupplied to separatehalves of a split-root system, however, cumulative uptake ofNH4+ was about half that of NO3. The uptake of NH4+,which is inhibited in nitrogen-depleted plants, thus is facilitatedby the presence of exogenous NO3, and the stimulatingeffect of NO3 on uptake of NH4+ appears to be confinedto processes within root tissues. In Experiment II, resupplyof nitrogen as both NH4+ and NO3 in a ratio of either1:1 or 9:1 enhanced the uptake of NH4+. The enhancement of NH4+uptake was 1.8-fold greater when the NH4+: NO3-resupplyratio was 1:1 than when it was 9:1; however, only 1.3 timesas much NO3 was taken up by plants resupplied with the1 :1 exogenous ratio. The effect of NO3 on enhancementof uptake of NH4+ apparently involves more than net uptake ofNO3 itself and perhaps entails an effect of NO3uptake on maintenance of K+ availability within the plant. Theconcentration of K+ in plants declined slightly during nitrogendeprivation and continued to decline following resupply of nitrogen.The greatest decline in K+ concentration occurred when nitrogenwas resupplied as NH4+ alone. It is proposed that decreasedavailability of K+ within the NH4+-resup-plied plants inhibitedNH4+ uptake through restricted transfer of amino acids fromthe root symplasm into the xylem. Key words: Ammonium, Glycine max, nitrate, nitrogen-nutrition, nitrogen stress, split-root cultures 相似文献
40.