全文获取类型
收费全文 | 1032篇 |
免费 | 49篇 |
国内免费 | 90篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 53篇 |
妇产科学 | 12篇 |
基础医学 | 106篇 |
口腔科学 | 24篇 |
临床医学 | 228篇 |
内科学 | 231篇 |
皮肤病学 | 80篇 |
神经病学 | 31篇 |
特种医学 | 75篇 |
外科学 | 104篇 |
综合类 | 62篇 |
预防医学 | 44篇 |
眼科学 | 8篇 |
药学 | 76篇 |
中国医学 | 3篇 |
肿瘤学 | 29篇 |
出版年
2021年 | 9篇 |
2019年 | 9篇 |
2018年 | 10篇 |
2017年 | 17篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 27篇 |
2013年 | 41篇 |
2012年 | 21篇 |
2011年 | 23篇 |
2010年 | 36篇 |
2009年 | 24篇 |
2008年 | 15篇 |
2007年 | 68篇 |
2006年 | 15篇 |
2005年 | 25篇 |
2004年 | 13篇 |
2003年 | 17篇 |
2002年 | 16篇 |
2001年 | 20篇 |
2000年 | 22篇 |
1999年 | 19篇 |
1998年 | 35篇 |
1997年 | 51篇 |
1996年 | 35篇 |
1995年 | 40篇 |
1994年 | 36篇 |
1993年 | 28篇 |
1992年 | 17篇 |
1991年 | 10篇 |
1990年 | 25篇 |
1989年 | 34篇 |
1988年 | 22篇 |
1987年 | 18篇 |
1986年 | 15篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 13篇 |
1977年 | 11篇 |
1976年 | 13篇 |
1975年 | 8篇 |
1972年 | 8篇 |
1968年 | 8篇 |
1966年 | 10篇 |
1965年 | 12篇 |
1963年 | 11篇 |
1959年 | 13篇 |
1956年 | 8篇 |
排序方式: 共有1171条查询结果,搜索用时 15 毫秒
31.
Jacopo Olivieri Federico Mosna Matteo Pelosini Angelo Fama Sara Rattotti Margherita Giannoccaro Giuseppe Carli Maria Chiara Tisi Simone Ferrero Nicola Sgherza Anna Maria Mazzone Dario Marino Teresa Calimeri Giacomo Loseto Francesco Saraceni Gabriella Tomei Simona Sica Giulia Perali Francesco Zaja 《Biology of blood and marrow transplantation》2018,24(9):1814-1822
BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM =?607, FEAM =?431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM?=?2011 versus FEAM?=?2013, P?<?.001), Sorror score ≥3 (BEAM?=?15% versus FEAM?=?10%, P?=?.017), and radiotherapy use (BEAM?=?18% versus FEAM?=?10%, P?<?.001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM?=?31% versus FEAM?=?44%, P?<?.001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM?=?.1 versus FEAM?=?.19, P?<?.001). Response status at day 100 post-ASCT (overall response: BEAM?=?91% versus FEAM?=?88%, P?=?.42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P?=?.04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply. 相似文献
32.
4分子治疗分析肿瘤细胞中的分子遗传性变异及后天变异的方法正在快速成熟起来。这些方法通常涉及基因组学、转录特征性识别及蛋白质组学,有利于更深入地了解ALL的发病机理,使用于临床评估的靶向治疗全面发展。最终,这些层出不穷的新技术将营造出一个全新的个性化分子医学时代,创造出效果更好而毒性更低的治疗方案。尽管治疗方案均显示了药物介入控制细胞周期进程、基因转录、细胞运动、凋亡及细胞代谢信号通路的可行性(图1),但针对ALL的分子治疗情况(表1)仍差强人意。我们将从众多正处于临床前期或早期临床研究的分子治疗方案中,选择出那… 相似文献
33.
Zaramella P Saraceni E Freato F Falcon E Suppiej A Milan A Laverda AM Chiandetti L 《Early human development》2007,83(8):483-489
BACKGROUND: Diagnostic tools of birth asphyxia provide only an uncertain prediction of neurological outcome. AIMS: To assess whether TOI and DeltaCBV, combined with a set of biochemical and neurophysiological variables, have any diagnostic and prognostic value in birth depression or asphyxia. STUDY DESIGN: Case control study at the nursery and NICU of the Padova University Children's Hospital. SUBJECTS: 22 term neonates with an Apgar score < or = 6 at 5', a 1-h umbilical artery pH value < or = 7.25 with an increased base deficit and a gestational age > or = 36 weeks; 15 healthy term infants with an Apgar score > or = 9 at 5'. OUTCOME MEASURES: Troponin I and NIRS measurements (TOI and DeltaCBV) were assessed in both groups. Blood gases, neurological evaluation, US, NIRS, EEG and SEP were evaluated in the infants with depression or asphyxia. RESULTS: Troponin I was higher in the study group than in controls (p=0.04), showing a correlation with base excess values. In the depressed/asphyxiated neonates with an abnormal outcome at 1 year, TOI rose to 80.1% vs 66.4% in controls (p=0.04) and 74.7% in infants with a normal 1-year outcome. A multiple regression model showed a significant multiple correlation coefficient, R=0.79, p<0.001, where the predictive variables significantly associated with outcome were SEP and BE. CONCLUSIONS: Troponin I is a useful short-term index of birth asphyxia or perinatal depression. An increased TOI suggests a risk of abnormal neurological outcome at 1 year. Among the cotside variables, BE and evoked potential abnormalities were the best predictors of abnormal outcome in this study. 相似文献
34.
Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts 总被引:4,自引:1,他引:4
Kilpatrick MW; Phylactou LA; Godfrey M; Wu CH; Wu GY; Tsipouras P 《Human molecular genetics》1996,5(12):1939-1944
The hammerhead ribozyme is a small catalytic RNA molecule. Potential
hammerhead ribozymes that possess a catalytic domain and flanking sequence
complementary to a target mRNA can cleave in trans at a putative cleavage
site within the target molecule. We have investigated the potential of
hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene
(FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of
the elastin-associated microfibrils. Mutations in the FBN1 gene are
responsible for Marfan syndrome (MFS), a common systemic disorder of the
connective tissue. Many FBN1 mutations responsible for MFS appear to act in
a dominant-negative fashion, raising the possibility that reduction of the
amount of product from the mutant FBN1 allele might be a valid therapeutic
approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to
the 5' end of the human FBN1 mRNA has been designed and synthesized, and
shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is
magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of
the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor-
mediated endocytosis of a ribozyme-transferrin-polylysine complex,
specifically reduces both cellular FBN1 mRNA and the deposition of
fibrillin in the extracellular matrix. These results suggest that the use
of hammerhead ribozymes is a valid approach to the study of fibrillin gene
expression and possibly to the development of a therapeutic approach to
MFS.
相似文献
35.
LYDIA L. NAKOPOULOU ANASTASIA ALEXIADOU GEORGE E. THEODOROPOULOS ANDREAS CH. LAZARIS ANASTASIA TZONOU ANDONIS KERAMOPOULOS 《The Journal of pathology》1996,179(1):31-38
The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10·7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression. 相似文献
36.
KJ Champion C Bunag AL Estep JR Jones CH Bolt RC Rogers KA Rauen DB Everman 《Clinical genetics》2011,79(5):468-474
Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation. 相似文献
37.
Hon YY; Fessing MY; Pui CH; Relling MV; Krynetski EY; Evans WE 《Human molecular genetics》1999,8(2):371-376
The molecular basis for the genetic polymorphism of thiopurine S -
methyltransferase (TPMT) has been estab-lished for Caucasians, but it
remains to be elucidated in African populations. In the current study, we
determined TPMT genotypes in a population of 248 African-Americans and
compared it with allele frequencies in 282 Caucasian Americans. TPMT
genotype was determined in all individuals with TPMT activity indicative of
a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n
= 21 Caucasians) and a control group with TPMT activity indicative of a
homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23
African-Americans, n = 21 Caucasians). No mutant alleles were found in the
high activity control groups. The overall mutant allele frequencies were
similar in African-Americans and Caucasians (4.6 and 3.7% of alleles,
respectively). However, while TPMT*3C was the most prevalent mutant allele
in African-Americans (52.2% of mutant alleles), it represented only 4.8% of
mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and
TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant
alleles), whereas TPMT*3A was the most prevalent mutant allele in
Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing
a single nucleotide transition (G644A), leading to an amino acid change at
codon 215 (Arg-->His), was found in one African-American with
intermediate activity. These data indicate that the same TPMT mutant
alleles are found in American black and white populations, but that the
predominant mutant alleles differ in these two ethnic groups.
相似文献
38.
K KANEKO Y SUZUKI T SHIMIZU Y YAMASHIRO K YABUTA CH LIFSCHITZ 《Journal of paediatrics and child health》1995,31(4):336-338
Objective: To investigate the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of ulcerative colitis (UC) in Japanese children.
Methodology Serum samples from 23 children with UC (17 Japanese, 6 non-Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese), 10 children with other diarrhoeal diseases, and 33 normal, healthy adult volunteers were assayed for ANCA using an indirect immunofluorescence technique.
Results ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in non-Japanese children. The difference in prevalence between Japanese and non-Japanese children with UC was not statistically significant ( P >0.05). ANCA were not found in other diarrhoeal patients and volunteers.
Conclusions Although ANCA have been reported to be useful in the diagnosis of UC in adults, they may be of limited use in Japanese children. This might reflect the heterogeneity of UC. 相似文献
Methodology Serum samples from 23 children with UC (17 Japanese, 6 non-Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese), 10 children with other diarrhoeal diseases, and 33 normal, healthy adult volunteers were assayed for ANCA using an indirect immunofluorescence technique.
Results ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in non-Japanese children. The difference in prevalence between Japanese and non-Japanese children with UC was not statistically significant ( P >0.05). ANCA were not found in other diarrhoeal patients and volunteers.
Conclusions Although ANCA have been reported to be useful in the diagnosis of UC in adults, they may be of limited use in Japanese children. This might reflect the heterogeneity of UC. 相似文献
39.