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1.
Bayrak S; Holmdahl R; Travers P; Lauster R; Hesse M; Dolling R; Mitchison NA 《International immunology》1997,9(11):1687-1699
Type II collagen (CII) is of immunological interest because of its
repetitive structure and properties as an autoantigen. The mouse gene has
recently been cloned, thus enabling T cell-defined epitopes to be
identified. Multiple novel epitopes on mouse CII are here detected in the
autoreactive T cell response. The major response is directed to an epitope
with residues 707-721 located on the CB10 fragment. Some 25 other epitopes
are also recognized, including the autologous homologue of the 256-270
epitope which dominates in the response to foreign collagen. The cells
reactive with mouse collagen peptides were of Th1 type, as judged by
release of IFN-gamma. No significant reactivity was detected to mouse CII
peptides during ongoing disease. Alignment of the mouse epitopes revealed a
sequence motif with characteristic side chains at residues P1, P4 and P7,
and to a lesser extent at P5, within a nonamer core sequence. Binding of
these epitopes was simulated in a computer model of the I-Aq molecule,
where peptides with anchor residues at P1, P4 and P7 were indeed found to
fit the binding groove best. The spacing of pockets and the fine structure
of the binding surface of the I-Aq molecule meshes with the repetitive
structure of the collagen (X-Y-Gly), thus providing a likely explanation
for the occurrence of multiple epitopes. Comparison with human DR binding
motifs showed that the I-Aq motif resembles most closely that of the DR4
subtypes which predispose for rheumatoid arthritis.
相似文献
2.
3.
北方汉族人群维生素D受体基因Bsm I位点多态性与前列腺癌易感性的相关性分析 总被引:1,自引:1,他引:0
目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。 方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。 结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。 结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。 相似文献
4.
Morphology of microparticles of the microencapsulated measles vaccine was studied by cryofractography, transmission electronic microscopy and by atomic force microscopy; co-polymers of polyacrylic acid and of sodium-alginate (spermidine) complexes were used as the matrix. The different-composition microcapsules had clear-cut borders and a certain range of sizes; but they were different in morphology, and their structures and densities varied identically with regard for a medium acidity, which is apparently preconditioned by some conformation-type alterations of matrix molecules. The studied preparations can, probably, protect the viral material in the stomach aggressive medium and release the material to ensure its contact with the intestine lymph tissue; thereof, they can be referred to as promising for further study of mucosal vaccines. 相似文献
5.
The morphology and virus localization were studied in the microcapsulated measles vaccine formulation involving polyacrylic acid (PAA) copolymers as a matrix. Transmission electron microscopy and phosphotungsic staining at a pH value of 2 to 7 showed that the morphology of microparticles was related to the value of pH and to the concentration of a polymer in the matrix. In the neutral medium, the microcapsules had the sizes of 0.5 to 10 microm, which were optimal for transport through the intestinal wall when immunization was orally used. Immunocytochemistry revealed measles virus antigen within the microparticles. The specific activity of the microcapsulated formulation of measles virus was as high as 3.36 and 4.31 lg of TCD50/0.5 ml for the samples containing 1 and 0.1% polymer, respectively. The findings suggest that the microparticles of the vaccine contain live measles virus. 相似文献
6.
Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy 总被引:7,自引:6,他引:7
While an unstable CTG triplet repeat expansion is responsible for myotonic
dystrophy, the mechanism whereby this genetic defect induces the disease
remains unknown. To detect proteins binding to CTG triplet repeats, we
performed bandshift analysis using as probes double- stranded DNA fragments
having CTG repeats [ds(CTG)6-10] and single- stranded oligonucleotides
having CTG repeats ss(CTG)8 or RNA CUG triplet repeats (CUG)8. The source
of protein was nuclear and cytoplasmic extracts of HeLa cells, fibroblasts
and myotubes. Proteins binding to the double-stranded DNA repeat
[ds(CTG)6-10], were inhibited by nonlabeled ds(CTG)6-10, but not by a
non-specific DNA fragment (USF/AD-ML). Another protein binding to ssCTG
probe and RNA CUG probe was inhibited by nonlabeled (CTG)8 and (CUG)8.
Nonlabeled oligos with different triplet repeat sequences, ss(CAG)8 or
ss(CGG)8, did not inhibit binding to the ss(CTG)8 probe. However, when
labeled as probes, the (CAG)8 and (CGG)8 bound to proteins distinct from
the CTG proteins and binding was inhibited by nonlabeled (CAG)8 or (CGG)8
respectively. The protein binding only to the RNA repeat (CUG)8 was
inhibited by nonlabeled (CUG)8 but not by nonlabeled single- or
double-stranded CTG repeats. Furthermore, the CUG-BP exhibited no binding
to an RNA oligonucleotide of triplet repeats of the same length but having
a different sequence, CGG. The CUG binding protein was localized to the
cytoplasm, whereas dsDNA binding proteins were localized to the nuclear
extract. Thus, several trinucleotide binding proteins exist and their
specificity is determined by the triplet sequence. The novel protein,
CUG-BP, is particularly interesting since it binds to triplet repeats known
to be present in myotonin protein kinase mRNA which is responsible for
myotonic dystrophy.
相似文献
7.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
8.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
9.
p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia, cirrhosis and hepatocellular carcinoma 总被引:2,自引:0,他引:2
I. OJANGUREN A. ARIZA E.M. CASTELLÀ A. FERNÁNDEZ-VASALO J.L. MATE J.J. NA VAS-PALACIOS 《Histopathology》1995,26(1):63-68
The prolonged half-life of mutant p53 makes feasible its immunocytochemical detection. In order to assess the pathogenetic role of mutant p53 in regenerative and neoplastc liver disease we studied its immunohistochemical expression in cases of hepatic cirrhosis, hepatocellular carcinoma (HCC), cirrhosis with areas of HCC, hepatocellular adenoma and focal nodular hyperplasia. The study included needle and wedge biopsies of 50 cirrhotic livers, 59 HCCs (36 of them with associated cirrhosis), six adenomas and two focal nodular hyperplasias. Sixty-five HCC fineneedle cytology specimens were also included in the study. There was no immunohistochemical evidence of mutant p53 expression in any of the cases of cirrhotic liver (except for one instance associated with HCC) adenoma or focal nodular hyperplasia. In contrast p53 was detected in 8.5% of HCC cases in the biopsy series and 24% of HCC cases in the fine needle aspiration series. In addition, mutant p53 expression in HCC was positively correlated with tumour grade. According to grade, the distribution of p53 positive immunoreactivity among HCCs was as follows: Grade I-II, 0% of cases in the biopsy series and 9% in the fine needle aspirates; Grade III, 18% in the biopsy series and 55% in the fine needle aspirates; and Grade IV, 40% in the biopsy series. Therefore, mutant p53 expression does not seem to be associated with benign liver lesions but seems to correlate with the progression of HCC through various grades of increasing malignancy. 相似文献
10.