全文获取类型
收费全文 | 3078篇 |
免费 | 339篇 |
国内免费 | 8篇 |
出版年
2021年 | 51篇 |
2020年 | 30篇 |
2019年 | 36篇 |
2018年 | 34篇 |
2017年 | 39篇 |
2016年 | 58篇 |
2015年 | 70篇 |
2014年 | 95篇 |
2013年 | 112篇 |
2012年 | 147篇 |
2011年 | 159篇 |
2010年 | 88篇 |
2009年 | 85篇 |
2008年 | 106篇 |
2007年 | 121篇 |
2006年 | 124篇 |
2005年 | 96篇 |
2004年 | 110篇 |
2003年 | 100篇 |
2002年 | 107篇 |
2001年 | 83篇 |
2000年 | 68篇 |
1999年 | 80篇 |
1998年 | 32篇 |
1997年 | 32篇 |
1996年 | 34篇 |
1994年 | 25篇 |
1992年 | 62篇 |
1991年 | 64篇 |
1990年 | 65篇 |
1989年 | 60篇 |
1988年 | 53篇 |
1987年 | 46篇 |
1986年 | 49篇 |
1985年 | 58篇 |
1984年 | 49篇 |
1983年 | 51篇 |
1982年 | 46篇 |
1981年 | 33篇 |
1980年 | 40篇 |
1979年 | 51篇 |
1978年 | 60篇 |
1977年 | 53篇 |
1976年 | 38篇 |
1975年 | 39篇 |
1974年 | 26篇 |
1973年 | 53篇 |
1972年 | 30篇 |
1971年 | 27篇 |
1968年 | 30篇 |
排序方式: 共有3425条查询结果,搜索用时 218 毫秒
71.
Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus 总被引:4,自引:0,他引:4
Most studies on the relationship of maternal diabetes to cardiovascular malformations (CVM) have been prospective investigations of pregnancy outcome and therefore could not identify associations with rare cardiac lesions. The results of a retrospective study shed new light on the risks of specific cardiac defects in diabetic pregnancies. The Baltimore-Washington Infant Study, a population-based case-control investigation of CVM, provides information on maternal diabetes reported in personal interviews. Among 2259 mothers of cases, 35 (1.5%) reported diabetes present before pregnancy (called "overt") and 95 (4.2%) reported diabetes only during pregnancy (called "gestational"). Among 2,801 mothers of controls, 14 (0.5%) had overt diabetes and 83 (3.0%) had gestational diabetes. Malformation-specific risks were expressed as odds ratios (OR) with 99.5% confidence intervals (CI). The strongest associations with overt maternal diabetes were found with double outlet right ventricle (OR 21.33; 99.5% CI 3.34, 136.26), and truncus arteriosus (OR 12.81; 99.5% CI 1.43, 114.64). No significant diagnosis-specific associations were found with gestational diabetes. Non-cardiac malformations were present in 23% of infants with CVM whose mothers had overt diabetes and in 26% of infants with CVM whose mother had gestational diabetes, in 32% of infants with CVM whose mothers did not have diabetes, and in 4% of controls. Double outlet right ventricle and truncus arteriosus are malformations dependent upon neural-crest-cell-derived ectomesenchymal tissues; these are precisely the conotruncal abnormalities that result from experimental ablation of the neural crest in chick embryos. The association with diabetes suggests a further etiologic link between these two lesions. 相似文献
72.
John F. Reinhard Jr. Emanuel J. Diliberto Jr. Alejandro J. Daniels 《Journal of neurochemistry》1989,52(4):1253-1259
Cultures of bovine adrenomedullary chromaffin cells accumulated 1-[methyl-3H]methyl-4-phenylpyridinium ([3H]MPP+) in a time- and concentration-dependent manner with an apparent Km of 0.7 microM and a Vmax of 3 pmol/min/10(6) cells. The uptake was sodium dependent and sensitive to inhibitors of the cell-surface catecholamine transporter. At low concentrations of MPP+, the subcellular distribution was identical to that of endogenous catecholamines in the catecholamine-containing chromaffin vesicles. However, at a higher concentration of MPP+, a larger proportion of the toxicant was recovered in the cytosolic fraction, with less in the chromaffin vesicle fractions. When cells were prelabeled with [3H]MPP+, at 1 and 300 microM, and then permeabilized with digitonin in the absence of Ca2+, there was a proportionally greater release of MPP+ from the cells labeled at the higher concentration of the toxicant. In the presence of Ca2+, cell permeabilization induced a time-dependent secretion of catecholamines and a parallel secretion of MPP+. Under these conditions, the secretion of endogenous catecholamines was unaffected by the presence of MPP+. When the permeabilization studies were carried out in the presence of tetrabenazine, a massive release of MPP+ was observed in the absence of Ca2+ and was not further increased by Ca2+. In intact cells prelabeled with 300 microM [3H]MPP+, the secretagogues nicotine and veratridine elicited a Ca2+ -dependent secretion of catecholamines and MPP+ from the cells in similar proportions to their cellular contents. Barium-induced release of both species was independent of external Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
73.
74.
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
75.
Ethanol inhibits thrombin-induced secretion by human platelets at a site distinct from phospholipase C or protein kinase C. 总被引:1,自引:0,他引:1 下载免费PDF全文
Ethanol is known to inhibit the activation of platelets in response to several physiological agonists, but the mechanism of this action is unclear. The addition of physiologically relevant concentrations of ethanol (25-150 mM) to suspensions of washed human platelets resulted in the inhibition of thrombin-induced secretion of 5-hydroxy[14C]tryptamine. Indomethacin was included in the incubation buffer to prevent feedback amplification by arachidonic acid metabolites. Ethanol had no effect on the activation of phospholipase C by thrombin, as determined by the formation of inositol phosphates and the mobilization of intracellular Ca2+. Moreover, ethanol did not interfere with the thrombin-induced formation of diacylglycerol or phosphatidic acid. Stimulation of platelets with phorbol ester (5-50 nM) resulted in 5-hydroxy[14C]tryptamine release comparable with those with threshold doses of thrombin. However, ethanol did not inhibit phorbol-ester-induced secretion. Ethanol also did not interfere with thrombin- or phorbol-ester-induced phosphorylation of myosin light chain (20 kDa) or a 47 kDa protein, a known substrate for protein kinase C. By electron microscopy, ethanol had no effect on thrombin-induced shape change and pseudopod formation, but prevented granule centralization and fusion. The results indicate that ethanol does not inhibit platelet secretion by interfering with the activation of phosphoinositide-specific phospholipase C or protein kinase C by thrombin. Rather, the data demonstrate an inhibition of a Ca2(+)-mediated event such as granule centralization. 相似文献
76.
Autoantibody to the nucleosome subunit (H2A-H2B)-DNA is an early and ubiquitous feature of lupus-like conditions 总被引:2,自引:0,他引:2
Chromatin, a huge polymer of nucleosomes, has been implicated as an important target of autoantibodies in idiopathic and drug-induced lupus for decades, but the antigenicity of chromatin has only recently been dissected. IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, is present in the majority of patients with systemic lupus erythematosus, in >90% of patients with lupus induced by procainamide and in individual patients with lupus induced by a variety of other drugs, but is not seen in people taking these medications who are clinically asymptomatic. Anti-[(H2A-H2B)-DNA] accounted for the bulk of the anti-chromatin activity in drug-induced lupus. The earliest detectable autoantibody in lupus-prone mice recognized similar epitopes in the (H2A-H2B)-DNA subnucleosome complex; as the immune response progressed, native DNA and other constituents of chromatin became antigenic. The importance of chromatin-reactive T cells in the anti-[(H2A-H2B)-DNA] response is suggested by the presence of somatic mutations in antibody VH and VL regions, their perdominant IgG isotype and the similarity in kinetics of their production to that of conventional T cell dependent antigens. Together with the serologic data from human lupus-like disease, these results are consistent with chromatin being a common stimulant for both B and T cells. While chromatin-reactive antibodies are closely associated with systemic disease and have recently been implicated in glomerulonephritis in SLE, the absence of renal disease in drug-induced lupus indicates that additional abnormalities are required to manifest the serious pathogenic potential of anti-[(H2A-H2B)-DNA] antibodies.Abbreviations APC
antigen present cells
- DIL
drug-induced lupus
- ELISA
enzyme-linked immunosorbent assay
- GBM
glomerular basement membrane
- [(H2A-H2B)-DNA]
an intermolecular complex consisting of DNA and a dimer of histones H2A and H2B
- nDNA
native (double-stranded) DNA
- SLE
systemic lupus erythematosus 相似文献
77.
Emanuel D. Rudolph 《American journal of botany》1996,83(5):661-671
The establishment of teaching laboratories for botany in the United States was strongly influenced in the early part of the 19th century by the founding of a laboratory of natural history at the Rensselaer School by Amos Eaton who inspired numerous educators, particularly women. By midcentury and later, botany programs were established at land-grant colleges and the so-called “new Botany” movement spread from them. In the latter part of the century additional changes were brought about by the influence of German laboratory activity and botanists’ reactions to the introduction of the Huxley-Martin biology programs to America. During these times, Americans were improving their own manufactured microscopes, laboratory supplies, and equipment capabilities. By the beginning of the 20th century, laboratory teaching of botanical subjects was widely accepted as normal in universities and colleges, as well as in some high schools. 相似文献
78.
Jeffrey S. Rubin Donald P. Bottaro Marcio Chedid Toru Miki Dina Ron Hyae-Gyeong Cheon William G. Taylor Emma Fortney Hiromi Sakata Paul W. Finch William J. LaRochelle 《Cell biology international》1995,19(5):399-411
Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex sterorid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis. 相似文献
79.
Structure of REC2, a recombinational repair gene of Ustilago maydis, and its function in homologous recombination between plasmid and chromosomal sequences. 总被引:2,自引:2,他引:0 下载免费PDF全文
Mutation in the REC2 gene of Ustilago maydis leads to defects in DNA repair, recombination, and meiosis. Analysis of the primary sequence of the Rec2 protein reveals a region with significant homology to bacterial RecA protein and to the yeast recombination proteins Dmc1, Rad51, and Rad57. This homologous region in the U. maydis Rec2 protein was found to be functionally sensitive to mutation, lending support to the hypothesis that Rec2 has a functional RecA-like domain essential for activity in recombination and repair. Homologous recombination between plasmid and chromosomal DNA sequences is reduced substantially in the rec2 mutant following transformation. The frequency can be restored to a level approaching, but not exceeding, that observed in the wild-type strain if transformation is performed with cells containing multiple copies of REC2. 相似文献
80.
Molecular characterization of the marker chromosome associated with cat eye syndrome. 总被引:8,自引:2,他引:6
A. J. Mears A. M. Duncan M. L. Budarf B. S. Emanuel B. Sellinger J. Siegel-Bartelt C. R. Greenberg H. E. McDermid 《American journal of human genetics》1994,55(1):134-142
Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study we have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2. 相似文献