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Cytostasis of different tumours by a murine PPD-reactive CD4+ T lymphocyte clone is mediated by interferon-gamma and tumour necrosis factor alone or synergistically. 总被引:1,自引:3,他引:1 下载免费PDF全文
M G Wing A M Montgomery C Harley P J Lachmann 《Clinical and experimental immunology》1990,82(2):208-213
We have shown that a murine CD4+ PPD-reactive T lymphocyte clone was weakly cytotoxic towards the syngeneic tumour B16 melanoma and MC6A fibrosarcoma which had been coated with PPD using a monoclonal antibody-PPD heteroconjugate. Cell-free supernatants produced by PPD-stimulated T lymphocyte clones were however highly cytostatic for the two tumour targets when assayed over 48-72 h. In this study we have demonstrated good titres of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) in the supernatants, which accounted for their observed cytostatic activity on the tumour targets. The high level of cytostasis seen with the B16 melanoma using the supernatants could be attributed to their sensitivity to the cytostatic activity of IFN-gamma; the lower levels of cytostasis seen with the IFN-gamma-resistant MC6A target was the result of IFN-gamma increasing the sensitivity of this target to TNF. Antibodies to IFN-gamma were able to neutralize the majority of the cytostatic activity of the supernatants on both targets, consistent with the role demonstrated for this lymphokine. 相似文献
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Antibody to donor HLA antigens is a significant barrier to both access to and outcome of allogeneic transplants. Many attempts have been made to desensitize patients with HLA-specific antibody, but the most effective and durable have been treatment with high-dose pooled human intravenous immunoglobulin (IVIg) and a combination of plasmapheresis and low-dose IVIg. Despite the success of these treatments, low levels of donor-specific antibody (DSA) persist in some patients. We examined factors that may be related to and used to predict the elimination of DSA. The most significant associations have been strength of antibody at initiation of treatment and antibody specificity, although other factors revealed a trend toward association. We demonstrate how the types of data generated here can be used to predict elimination or persistence of DSA. 相似文献
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Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically 下载免费PDF全文
Montgomery E Argani P Hicks JL DeMarzo AM Meeker AK 《The American journal of pathology》2004,164(5):1523-1529
Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas. 相似文献
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Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome 总被引:3,自引:4,他引:3
Sirotkin H; Morrow B; DasGupta R; Goldberg R; Patanjali SR; Shi G; Cannizzaro L; Shprintzen R; Weissman SM; Kucherlapati R 《Human molecular genetics》1996,5(5):617-624
Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are
developmental disorders characterized by a spectrum of phenotypes including
velopharyngeal insufficiency, conotruncal heart defects and facial
dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS
patients are hemizygous for a portion of chromosome 22. It is likely that
the genes encoded by this region play a role in the etiology of the
phenotypes associated with the disorders. Using a cDNA selection protocol,
we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS
minimally deleted interval. The cDNA encodes a protein of 1638 amino acids.
CLTD shares significant homology, but is not identical to the ubiquitously
expressed clathrin heavy chain gene. The CLTD gene also shows a unique
pattern of expression, having its maximal level of expression in skeletal
muscle. Velopharyngeal insufficiency and muscle weakness are common
features of VCFS patients. Based on the location and expression pattern of
CLTD, we suggest hemizygosity at this locus may play a role in the etiology
of one of the VCFS-associated phenotypes.
相似文献
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