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991.
Goffe B Papp K Gratton D Krueger GG Darif M Lee S Bozic C Sweetser MT Ticho B 《Clinical therapeutics》2005,27(12):1912-1921
BACKGROUND: Information on longer-term safety and tolerability is needed to confidently prescribe alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses. OBJECTIVE: The aim of this work was to further examine the safety profile of alefacept by integrating data from clinical trials involving patients with chronic plaque psoriasis who received up to 9 courses of therapy over a 5-year period. METHODS: Data from 13 clinical trials conducted in patients with plaque psoriasis were integrated because they had similar inclusion/exclusion criteria and assessments. Patients who enrolled in the analyzed trials were aged > or =15 years with chronic plaque psoriasis for > or =12 months that involved > or =10% of body surface area, and CD4+ T lymphocyte counts above the lower limit of normal (>404 cells/microL). The incidences of adverse events (AEs), serious AEs, discontinuations for AEs, infections, serious infections, malignancies, and anti-alefacept antibodies were summarized for each course of alefacept. The incidence of infections was stratified according to CD4+ T lymphocyte counts (<250 cells/microL vs > or =250 cells/microL). RESULTS: Data from 13 clinical trials of alefacept were integrated and summarized (multicenter, randomized, double-blind studies, n = 6; multicenter, open-label studies, n = 5; other, n = 2). The analyzed population (n = 1869) included 1291 (69.1%) men and 578 (30.9%) women, between the ages of 15 and 84 years (mean, 44.8 years), of whom 1648 (88.2%) were white. Weights ranged from 40 kg to 206 kg (mean, 90.0 kg). A total of 1369 of these patients had been included in a previous analysis. Among the most commonly reported AEs in each treatment course were headache (0%-14.2%), nasopharyngitis (7.7%-25.0%), influenza (0%-8.1%), upper respiratory tract infection (0%-12.5%), and pruritus (0%-7.5%). The rates of discontinuations due to AEs (0%-4.8%), serious AEs (0%-4.8%), serious infections (0%-0.9%), or malignancies (0%-4.8%) did not appear to increase with repeated exposure. Fewer than 1 % of patients in each course developed a serious infection. No opportunistic infections or infection-related deaths were reported. The incidence of infections appeared to be unrelated to CD4+ T lymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy. CONCLUSIONS: This integrated analysis of data from 13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis. 相似文献
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Combination therapy for moderate to severe psoriasis is often used to enhance efficacy and minimize treatment-related side effects; however, data are limited on combination therapy with the newer biologic agents. The current study examined patients who received alefacept in combination with ultraviolet B phototherapy as part of an international, open-label study evaluating up to 3 courses of alefacept in combination with other psoriasis therapies. Physician Global Assessment [corrected] scores improved by [greater than or equal to] 1 category in 88% [corrected] of patients and by [greater than or equal to] 2 categories in 76% [corrected] of patients in course A; [corrected] corresponding response rates were 100% and 55% in Course [corrected] B, and 85% and 77% in Course [corrected] C. At week 14, a PGA of "almost clear" or "clear" was achieved by 13%, 14%, and 8% of patients in courses A, B, and C, respectively. There was no evidence of a cumulative effect on T cells after multiple courses of therapy. The combination of alefacept and ultraviolet B was well tolerated and provided improvement in psoriasis. 相似文献
995.
Lila J. Finney Rutten Robert M. Jacobson Patrick M. Wilson Debra J. Jacobson Chun Fan John B. Kisiel Seth Sweetser Sidna M. Tulledge-Scheitel Jennifer L. St. Sauver 《Mayo Clinic proceedings. Mayo Clinic》2017,92(5):726-733
Objectives
To characterize early adoption of a novel multitarget stool DNA (MT-sDNA) screening test for colorectal cancer (CRC) screening and to test the hypothesis that adoption differs by demographic characteristics and prior CRC screening behavior and proceeds predictably over time.Patients and Methods
We used the Rochester Epidemiology Project research infrastructure to assess the use of the MT-sDNA screening test in adults aged 50 to 75 years living in Olmsted County, Minnesota, in 2014 and identified 27,147 individuals eligible or due for screening colonoscopy from November 1, 2014, through November 30, 2015. We used electronic Current Procedure Terminology and Health Care Common Procedure codes to evaluate early adoption of the MT-sDNA screening test in this population and to test whether early adoption varies by age, sex, race, and prior CRC screening behavior.Results
Overall, 2193 (8.1%) and 974 (3.6%) individuals were screened by colonoscopy and MT-sDNA, respectively. Age, sex, race, and prior CRC screening behavior were significantly and independently associated with MT-sDNA screening use compared with colonoscopy use after adjustment for all other variables (P<.05 for all). The rates of adoption of MT-sDNA screening increased over time and were highest in those aged 50 to 54 years, women, whites, and those who had a history of screening. The use of the MT-sDNA screening test varied predictably by insurance coverage. The rates of colonoscopy decreased over time, whereas overall CRC screening rates remained steady.Conclusion
The results of the present study are generally consistent with predictions derived from prior research and the diffusion of innovation framework, pointing to increasing use of the new screening test over time and early adoption by younger patients, women, whites, and those with prior CRC screening. 相似文献996.
Structural and mutational analysis of a conserved gene (DGSI) from the minimal DiGeorge syndrome critical region 总被引:2,自引:1,他引:2
Gong W; Emanuel BS; Galili N; Kim DH; Roe B; Driscoll DA; Budarf ML 《Human molecular genetics》1997,6(2):267-276
The majority of patients with DiGeorge syndrome (DGS), velocardiofacial
syndrome (VCFS), conotruncal anomaly face syndrome (CTAFS) and some
individuals with familial or sporadic conotruncal cardiac defects have
hemizygous deletions of chromosome 22. Most patients with these disorders
share a common large deletion, spanning > 1.5 Mb within 22q11.21-q11.23.
Recently, the smallest region of deletion overlap has been narrowed to a
250 kb area, the minimal DGS critical region (MDGCR), which includes the
locus D22S75 (N25). We have isolated and characterized a novel, highly
conserved gene, DGSI, within the MDGCR. DGSI has 10 exons and nine introns
encompassing 1702 bp of cDNA sequence and 11 kb of genomic DNA. The encoded
protein has 476 amino acids with a predicted mol. wt of 52.6 kDa. The
intron-exon boundaries have been analyzed and conform to the consensus
GT/AG motif. The corresponding murine Dgsi has been isolated and localized
to proximal mouse chromosome 16. The mouse gene contains the same number of
exons and introns, and the predicted protein has 479 amino acids with 93.2%
identity to that of the human DGSI gene. By database searching, both genes
have significant homology to a Caenorhabditis elegans hypothetical protein,
F42H10.7. Further, mutation analysis has been performed in 16 patients, who
have no detectable 22q11.2 deletion and some of the characteristic clinical
features of DGS/VCFS. We have detected eight sequence variants in DGSI.
These occurred in the 5'- untranslated region, the coding region and the
intronic regions adjacent to the intron-exon boundaries of the gene. Seven
of the eight variants were also present in normal controls or unaffected
family members, suggesting they may not be of etiologic significance.
相似文献
997.
998.
Sweetser DA Peniket AJ Haaland C Blomberg AA Zhang Y Zaidi ST Dayyani F Zhao Z Heerema NA Boultwood J Dewald GW Paietta E Slovak ML Willman CL Wainscoat JS Bernstein ID Daly SB 《Genes, chromosomes & cancer》2005,44(3):279-291
Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AML1/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLN1, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML. 相似文献
999.
1000.
Kelly CL; Rhead WJ; Kutschke WK; Brix AE; Hamm DA; Pinkert CA; Lindsey JR; Wood PA 《Human molecular genetics》1997,6(9):1451-1455
We report the therapeutic effects of liver-specific expression of a
short-chain acyl-CoA dehydrogenase (SCAD) transgene in the SCAD- deficient
mouse model. Transgenic mice were produced with a rat albumin
promoter/enhancer driving a mouse SCAD minigene (ALB-SCAD) on both the SCAD
normal genetic background and a SCAD-deficient background. In three
transgenic lines produced on the SCAD-deficient background, recombinant
SCAD activity and antigen in liver mitochondria were found up to 7-fold of
normal control values. All three lines showed a markedly reduced organic
aciduria and fatty liver, which are sensitive indicators of the metabolic
abnormality seen in this disease found in children. We found no detrimental
effects of high liver SCAD expression in transgenic mice on either
background. These studies provide important basic and practical therapeutic
information for the potential gene therapy of nuclear-encoded mitochondrial
enzyme deficiencies, as well as insights into the mechanisms of the
disease.
相似文献