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33.
Campath-1M--prophylactic use after kidney transplantation. A randomized controlled clinical trial 总被引:3,自引:0,他引:3
P J Friend G Hale H Waldmann S Gore S Thiru V Joysey D B Evans R Y Calne 《Transplantation》1989,48(2):248-253
Campath-1M is a rat monoclonal IgM antibody that binds human complement and recognizes virtually all peripheral human mononuclear cells. It is known to be effective in T cell depletion of bone marrow grafts, and encouraging results were obtained in a pilot study in which the antibody was used in prevention and treatment of rejection of kidney, pancreas, and liver allografts. In this randomized controlled clinical trial, Campath-1M has been evaluated as a prophylactic agent following renal allografting. It is shown that patients who received a 10-day course of the antibody immediately postoperatively, in addition to standard therapy with high-dose cyclosporine (17 mg/kg), experienced a significantly lower incidence of early acute cellular rejection than control patients who received cyclosporine alone. There was no evidence of "rebound" rejection following the end of antibody treatment to suggest that rejection had merely been delayed. However, patients who received this additional immunosuppression experienced a significantly higher incidence of serious infections than controls, this negating any benefit from the treatment in terms of graft survival. Thus, a monoclonal antibody of broad specificity directed against lymphocytes may be effective as a prophylactic agent after organ transplantation but its use should be accompanied by a reduction in other immunosuppressive drugs. 相似文献
34.
Verschuren MC; Blom B; Bogers AJ; Spits H; van Dongen JJ 《International immunology》1998,10(12):1873-1880
Recombination of deltaRec to psiJalpha will delete the TCR delta gene,
which is thought to play an important role in the bifurcation of the TCR
alphabeta versus TCR gammadelta differentiation lineages. We recently
detected a DNA-binding protein in human thymocytes, the so- called PJA-BP,
which recognizes the psiJalpha gene segment and might be one of the factors
involved in the regulation of preferential deltaRec- psiJalpha
rearrangements. We now investigate PJA-BP expression and its correlation
with TCR delta gene deletion in thymocytes. Our electrophoretic mobility
shift assay experiments showed that the PJA-BP is evolutionary conserved in
human, murine and simian thymocytes. Using a large series of human
hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is
thymocyte specific and seems to be restricted to thymocytes committed to
the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte
subpopulations showed that preferential deltaRec-psiJalpha rearrangements
as well as PJA-BP expression can be detected from the immature
CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage
onwards. These experiments indicate that expression of PJA-BP in human
thymocytes starts simultaneously with preferential deltaRec-psiJalpha
rearrangements, which supports our hypothesis that PJA-BP is one of the
factors involved in the preferential recombination of deltaRec to
psiJalpha.
相似文献
35.
Cody JD Semrud-Clikeman M Hardies LJ Lancaster J Ghidoni PD Schaub RL Thompson NM Wells L Cornell JE Love TM Fox PT Leach RJ Kaye CI Hale DE 《American journal of medical genetics. Part A》2005,137(1):9-15
Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals. 相似文献
36.
Gregory A Hale Laura C Bowman Richard J Rochester Eli Benaim Helen E Heslop Robert A Krance Edwin M Horwitz John M Cunningham Xin Tong Deo Kumar Srivastava Rupert Handgretinger Deborah P Jones 《Biology of blood and marrow transplantation》2005,11(11):912-920
Hemolytic uremic syndrome (HUS) is an uncommon but potentially life-threatening complication of hematopoietic stem cell transplantation. We retrospectively studied the medical records of 293 children who underwent allogeneic bone marrow transplantation at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of and to identify risk factors for transplant-associated HUS. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation for patients with hematologic malignancies (n = 244); patients with nonmalignant diseases (n = 49) received disease-specific regimens. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. HUS developed in 28 (9.6%) patients at a median of 171 days after transplantation. We identified older donor age (P = .029), use of antithymocyte globulin in the conditioning regimen (P = .008), and recipient CMV seronegativity (P = .011) as being associated with an increased risk of HUS. With a multiple regression analysis, the use of antithymocyte globulin (beta = .86; P = .04) and recipient cytomegalovirus seronegativity (beta = .93; P = .035) remained significant risk factors for the development of HUS. 相似文献
37.
Del-Favero J; Krols L; Michalik A; Theuns J; Lofgren A; Goossens D; Wehnert A; Van den Bossche D; Van Zand K; Backhovens H; van Regenmorter N; Martin JJ; Van Broeckhoven C 《Human molecular genetics》1998,7(2):177-186
Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was
previously mapped by linkage analysis studies to chromosome 3p12- p21.1
(SCA7). Positional cloning efforts have recently identified a novel gene,
SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We
cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig
spanning the SCA7 candidate region. Using a combination of genomic
sequencing and cosmid-based exon trapping, two expressed sequence tags were
identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis
identified the full- length SCA7 cDNA. Together, our sequence data defined
the intron/exon boundaries of the first two coding exons of the SCA7 gene,
with the first exon containing the expanded CAG repeat. Further, sequence
comparison with the published SCA7 cDNA identified one additional putative
exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the
YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one
extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at
least 55 repeats with allele lengths being inversely correlated with onset
age of ADCAII symptoms. The SCA7 repeats increased in length in successive
generations. Normal alleles had from four to 18 repeats, with 10 repeats
being the most common allele.
相似文献
38.
K. M. Mitchell R. J. Hale C. H. Buckley H. Fox D. Smith 《Virchows Archiv : an international journal of pathology》1993,422(5):357-360
An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean –3.709,P=0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker. 相似文献
39.
Guiying Nie Kathryn Hale Ying Li Ursula Manuelpillai Euan M Wallace Lois A Salamonsen 《Developmental dynamics》2006,235(12):3448-3455
Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternal-trophoblast interface suggests that HtrA1 may play a role in placental development. 相似文献
40.