全文获取类型
收费全文 | 287329篇 |
免费 | 21899篇 |
国内免费 | 8031篇 |
专业分类
耳鼻咽喉 | 1907篇 |
儿科学 | 3818篇 |
妇产科学 | 4120篇 |
基础医学 | 30859篇 |
口腔科学 | 4744篇 |
临床医学 | 20393篇 |
内科学 | 33087篇 |
皮肤病学 | 3326篇 |
神经病学 | 15959篇 |
特种医学 | 7871篇 |
外国民族医学 | 9篇 |
外科学 | 20879篇 |
综合类 | 46921篇 |
现状与发展 | 29篇 |
一般理论 | 15篇 |
预防医学 | 21996篇 |
眼科学 | 3502篇 |
药学 | 34700篇 |
194篇 | |
中国医学 | 47343篇 |
肿瘤学 | 15587篇 |
出版年
2024年 | 1084篇 |
2023年 | 4027篇 |
2022年 | 8483篇 |
2021年 | 11637篇 |
2020年 | 10183篇 |
2019年 | 10741篇 |
2018年 | 9946篇 |
2017年 | 10991篇 |
2016年 | 10368篇 |
2015年 | 9579篇 |
2014年 | 15344篇 |
2013年 | 18189篇 |
2012年 | 16677篇 |
2011年 | 18659篇 |
2010年 | 13386篇 |
2009年 | 11743篇 |
2008年 | 12703篇 |
2007年 | 13942篇 |
2006年 | 12733篇 |
2005年 | 11571篇 |
2004年 | 9738篇 |
2003年 | 8739篇 |
2002年 | 7109篇 |
2001年 | 6268篇 |
2000年 | 5251篇 |
1999年 | 4354篇 |
1998年 | 3407篇 |
1997年 | 3451篇 |
1996年 | 3005篇 |
1995年 | 2749篇 |
1994年 | 2591篇 |
1993年 | 2136篇 |
1992年 | 2008篇 |
1991年 | 1880篇 |
1990年 | 1568篇 |
1989年 | 1286篇 |
1988年 | 1253篇 |
1987年 | 1099篇 |
1986年 | 1026篇 |
1985年 | 2029篇 |
1984年 | 2150篇 |
1983年 | 1638篇 |
1982年 | 1675篇 |
1981年 | 1520篇 |
1980年 | 1419篇 |
1979年 | 1253篇 |
1978年 | 991篇 |
1977年 | 717篇 |
1976年 | 797篇 |
1975年 | 629篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
凋亡抑制蛋白XIAP和促凋亡因子Smac在胰腺癌化疗抵抗中的作用 总被引:5,自引:0,他引:5
目的探讨x-相关凋亡抑制蛋白(XIAP)和促凋亡因子Smac在胰腺癌细胞化疗抵抗中的作用,以及转染胞浆表达型Smac基因靶向下凋XIAP对化疗药物诱导的胰腺癌细胞凋亡的影响。方法应用流式细胞术检测顺铂、5-FU介导的Panc-1、BXPC-3的凋亡率及胞浆染色分析细胞XIAP表达变化,Western blot分析XIAP、Smac、Caspase-3表达水平;构建pEGFP-NI/Smac真核表达载体并转染胰腺癌Panc-1细胞,流式细胞术检测转染Smac基因前后Panc-1细胞的凋亡敏感性。结果与BXPC-3细胞相比,Panc-1对顺铂或5-FU介导的凋亡具有较强抵抗性,Western blot分析显示Panc-1细胞高表达XIAP,在化疗药物作用下化疗敏感细胞BXPC-3胞浆内XIAP水平下降明显多于Panc-1细胞,而且凋亡的BXPC-3细胞释放入胞浆内的成熟Smac蛋白水平明显高于Panc-1细胞。转染胞浆表达型Smac基因至化疗抵抗Panc-1细胞,可明显下调其XIAP表达水平,促进效应Caspase-3分子活化,显著提高顺铂、5-FU诱导的细胞凋亡率。结论胰腺癌细胞XIAP的表达水平下调与其化疗敏感性有关,XIAP是克服化疗抵抗的重要靶分子,而上调Smac活性蛋白的胞浆表达作为一种有效调节信号,通过拮抗XIAP的凋亡抑制作用协同化疗药物促进胰腺癌细胞凋亡。 相似文献
992.
The genome of equine arteritis virus (EAV) produces a 3 coterminal-nested set of six subgenomic (sg) viral RNAs during virus replication cycle, and each set possesses a common leader sequence of 206 nucleotides (nt) in length derived from the 5 end of the viral genome. Given the presence of the leader region within both genomic and sg mRNAs, it is likely to contain cis-acting signals that may interact with cellular or viral proteins for RNA synthesis. Gel mobility shift assays indicated that proteins in Vero cell cytoplasmic extracts formed complexes with the positive (+) and negative (-) strands of the EAV leader RNA. Several cell proteins with molecular masses ranging from 74 to 31 kDa and 58 to 32 kDa were detected in UV-induced cross-linking assays with the EAV leader RNA (+) and (-) strands, respectively. In both cases, intense bands were observed at the 58–52 kDa molecular weight markers. Results from competition gel mobility shift assays using overlapping cold RNA probes spanning the leader RNA (+) strand indicated that nt 140–206 are not necessary for binding to cell proteins. 相似文献
993.
Imai K Zhu Y Revy P Morio T Mizutani S Fischer A Nonoyama S Durandy A 《Clinical immunology (Orlando, Fla.)》2005,115(3):277-285
Autosomal recessive form of hyper-IgM syndrome type 2 (AR-HIGM2) is secondary to mutations affecting both alleles of AICDA gene encoding activation-induced cytidine deaminase, characterized by defects of immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in most of the patients. We herein report the immunological phenotype of seven patients carrying a single heterozygous R190X mutation in AICDA. Variable defect in in vivo CSR inherited as an autosomal dominant (AD) trait strongly suggests that this heterozygous AICDA mutation causes HIGM (AD-HIGM2). In AD-HIGM2 B cells, CSR was consistently found impaired in vitro. However, in contrast to AR-HIGM2, the CSR-induced double-stranded DNA breaks in the switch region of IgM heavy chain gene were detected. The SHM frequency in V regions of IgM heavy chain gene in B cells was normal in all (but one patient). The characteristics of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR. 相似文献
994.
Misawa A Hosoi H Imoto I Iehara T Sugimoto T Inazawa J 《Journal of human genetics》2004,49(10):586-589
Malignant rhabdoid tumor (MRT) is a highly malignant pediatric cancer, which arises in various sites such as the kidney, brain, and soft tissues. Cytogenetic studies have revealed alterations of 22q11 in MRT. Recently, deletions and mutations of the SNF5/INI1 locus in 22q11.2 have been reported in MRT, suggesting that SNF5/INI1 is a tumor suppressor gene for MRT. Here we report our molecular cytogenetic study for a newly established cell line from extrarenal MRT with t(1;22)(p36;q11.2). Consequently, the reciprocal translocation was associated with the interstitial deletion of a small segment including SNF5/INI1, and another, chromosome 22, showed terminal deletion, the breakpoint of which was located 70–80 kb centromeric to SNF5/INI1, resulting in homozygous deletion of SNF5/INI1 in this cell line. 相似文献
995.
氨基胍对去卵巢大鼠主动脉晚期糖化终末产物及血脂的影响 总被引:2,自引:1,他引:2
将 6月龄雌性SD大鼠随机分为假手术组 (sham)、去卵巢组 (OVX)和去卵巢 +氨基胍组 (OVX +AG)。去除双侧卵巢 2周后用氨基胍治疗 13周。禁食 2 4h ,放血处死动物 ,取血和主动脉 ,分别测定主动脉AGEs、血脂和血清过氧化物含量。结果表明 ,与假手术组比较 ,去卵巢组主动脉AGEs、甘油三脂 (TG)、氧化低密度脂蛋白 (OX LDL)、丙二醛 (MDA)均明显升高 (分别为P <0 0 1,P <0 0 5 ,P <0 0 5和P <0 0 1) ;高密度脂蛋白 胆固醇 (HDL C)、载脂蛋白AⅠ (apo AⅠ )和超氧化物歧化酶 (SOD)活性均显著降低 (均P <0 0 1)。氨基胍组与病理组比较 ,主动脉AGEs、血清TG、MDA和OX LDL均明显降低 (分别为P <0 0 1,P <0 0 5、P <0 0 5和P <0 0 1) ;HDL C、apo AⅠ和SOD活性均显著升高 (均P <0 0 1)。提示氨基胍通过降低去卵巢大鼠主动脉AGEs含量 ,降低大鼠血清OX LDL和TG水平 ,升高HDL C、apo AⅠ水平和SOD活性 ,发挥其对心血管的保护作用 相似文献
996.
中国人群DXS102座位多态性鉴定及其应用 总被引:13,自引:0,他引:13
目的探讨中国人群中DXS102座位的多态分布。方法应用PCR扩增片段长度多态性(Amp-FLP)研究了无亲缘关系的234条X染色体。结果DXS102座位等位片段有8个,核心单元AC二核苷酸重复数为13~21,频率分布在0.013~0.156之间,杂合度观察值和无偏估测值分别为0.87和0.80,多态信息含量(PIC)0.80,女性基因型数为22个,男性基因型数为8个,该座位多态分布符合Hardy-Weinberg平衡定律。DXS102座位在中国人群和欧洲人群的分布有明显的种族差异,在中国人群中发现了两个新的等位片段。应用DXS102座位的短串联重复序列多态性对一接受基因治疗的血友病B家系进行分析和携带者筛查。结论DXS102座位连锁分析有望成为一种有效的血友病B基因诊断的方法。 相似文献
997.
The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE) has been reported to be an independent risk factor for myocardial infarction (MI), particularly in people lacking traditional risk factors. Furthermore, a borderline association between Lp(a) lipoprotein level and the I/D polymorphism at the ACE locus was reported in one study. We have searched for possible "level gene" or "variability gene" effects of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A-I (apoA-I), and body mass index (BMI). None of these variables differed significantly between genotypes in the I/D polymorphism in any of three population samples. A single population sample created by combining the three series, exhibited an insignificant trend towards individuals carrying the D-allele having a higher level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a significantly higher Lp(a) lipoprotein level than the combined group of ID/II individuals (p = 0.03). These results may indicate that the D-allele of the I/D polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein. 相似文献
998.
Analysis of the mechanism of lipoprotein(a) assembly 总被引:2,自引:0,他引:2
Marlys L. Koschinsky Santica M. Marcovina Lorraine F. May Brent R. Gabel 《Clinical genetics》1997,52(5):338-346
We have assessed the ability of a battery of purified recombinant apolipoprotein(a) (r-apo(a)) derivatives to bind to immobilized low-density lipoprotein (LDL) by ELISA. Removal of the apo(a) kringle IV type 8 and type 9 sequences dramatically reduced apo(a) binding to LDL. The binding of apo(a) to LDL was effectively inhibited by arginine, lysine, the lysine analogue ε-aminocaproic acid and proline; comparable inhibition was observed using the 17K and KIV5–8 r-apo(a) derivatives, suggesting a direct role for sequences contained in the latter species in mediating the initial non-covalent interactions which precede specific disulfide bond formation. We also determined that r-apo(a) binds directly to a synthetic apoB peptide spanning amino acid residues 3732–3745; this interaction appeared to be mediated by sequences present in apo(a) kringle IV types 8 and 9, and could be inhibited by arginine, lysine and proline. The results of this study indicate that the efficiency of Lp(a) assembly is a direct function of the initial non-covalent interactions between apo(a) and LDL; in addition, these studies suggest that Cys3734 in apoB mediates covalent linkage with apo(a) by virtue of the ability of the apoB sequences surrounding this residue to directly interact with apo(a) KIV type 9. 相似文献
999.
Henrik Husby Borghild Roald Rune Schjetlein Britt-Igjerd Nesheim Kåre Berg 《Clinical genetics》1996,50(1):47-49
We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined. 相似文献
1000.
Zvi Borochowitz Lorenzo Pavone Galia Mazor Renata Rizzo Hanna Dar 《American journal of medical genetics. Part A》1992,43(4):678-685
Five unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio-cutaneous-skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested. © 1992 Wiley-Liss, Inc. 相似文献