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81.
Gemins modulate the expression and activity of the SMN complex 总被引:1,自引:0,他引:1
Feng W Gubitz AK Wan L Battle DJ Dostie J Golembe TJ Dreyfuss G 《Human molecular genetics》2005,14(12):1605-1611
Reduction in the expression of the survival of motor neurons (SMN) protein results in spinal muscular atrophy (SMA), a common motor neuron degenerative disease. SMN is part of a large macromolecular complex (the SMN complex) that includes at least six additional proteins called Gemins (Gemin2-7). The SMN complex is expressed in all cells and is present throughout the cytoplasm and in the nucleus where it is concentrated in Gems. The SMN complex plays an essential role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs. To study the roles of the individual proteins, we systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA interference. We show that the reduction of SMN leads to a decrease in snRNP assembly, the disappearance of Gems, and to a drastic reduction in the amounts of several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the activity of the SMN complex. These findings demonstrate that other components of the SMN complex, in addition to SMN, are critical for the activity of the complex and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as well as potential disease genes for non-SMN motor neuron diseases. 相似文献
82.
83.
Igarashi S; Takiyama Y; Cancel G; Rogaeva EA; Sasaki H; Wakisaka A; Zhou YX; Takano H; Endo K; Sanpei K; Oyake M; Tanaka H; Stevanin G; Abbas N; Durr A; Rogaev EI; Sherrington R; Tsuda T; Ikeda M; Cassa E; Nishizawa M; Benomar A; Julien J; Weissenbach J; Tsuji S 《Human molecular genetics》1996,5(7):923-932
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative
disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at
14q32.1. To identify elements affecting the intergenerational instability
of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the
3' end of the CAG repeat affects intergenerational instability of the CAG
repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were
found to result in significantly greater instability of the CAG repeat
compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded
(CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic
regression analysis revealed that the relative risk for a large
intergenerational change in the number of CAG repeat units (< -2 or >
2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal
transmission than in that of maternal transmission and 7.4-fold (95% CI:
2.4-23.3) higher in the case of transmission from a parent with the
[expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of
transmission from a parent with the [expanded (CAG)n-CGG]/[normal
(CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The
combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal
(CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase
in the relative risk compared with that of maternal transmission and the
[expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal
(CAG)n-GGG] haplotypes. The results suggest that an inter- allelic
interaction is involved in the intergenerational instability of the
expanded CAG repeat.
相似文献
84.
应用Northern杂交技术,从表达序列标记(Expressedsequencetag,EST)克隆中筛选出一个在肝癌组织内高表达,而在相应癌旁肝及正常肝组织内低表达或不表达的基因片段。DNA序列测定表明,该基因片段为一未知新基因的部分序列。此基因片段可作为探针,进一步筛选cDNA文库,以得到新的癌基因的候选基因。 相似文献
85.
Jaccard J McDonald R Wan CK Guilamo-Ramos V Dittus P Quinlan S 《Journal of health psychology》2004,9(6):699-712
Accuracy of recall of the number of sexual partners individuals had over a period of one month, three months, six months and one year was studied in a group of 285 young, single, heterosexual adults. Self-reports of the number of partners were obtained on a weekly basis and then compared with recall of behavior over longer time periods that overlapped the weekly measures. For individuals who claimed abstinence or who claimed to be monogamous, accuracy of recall was relatively high, especially at the shorter time frames. Level of education was related to accuracy for claimed abstainers, such that lower levels of education were associated with lower accuracy of recall. Accuracy rates for individuals who reported having multiple sexual partners tended to be lower and were found to be related to one's propensity to engage in casual sex. 相似文献
86.
SARS病毒S1蛋白重组C端片段免疫效果的实验研究 总被引:1,自引:0,他引:1
为获得纯化的重组SARS病毒S1蛋白C端 ,研究其刺激机体产生针对SARS病毒免疫应答的规律和机制 ,将编码SARS病毒S1蛋白C端 311个氨基酸残基的基因克隆 ,并在原核表达系统中表达 ,纯化获得了的重组蛋白。利用SARS患者恢复期的血清 ,对纯化的重组S1蛋白进行血清学分析。结果表明 ,本研究中克隆表达的重组蛋白序列与公布的SARS病毒S1蛋白C端的序列相同 ,其编码的重组蛋白相对分子质量约为 5 90 0 0Mr。SARS患者恢复期的血清均与重组蛋白反应 ,在5 9 0 0 0Mr处形成特异性的反应条带 ,而来自SARS流行前的正常人对照血清则不能与重组蛋白反应。在本研究中获得的重组蛋白可以为研究SARS病毒识别宿主细胞受体的过程及其机制提供条件。 相似文献
87.
Chien-Chuan Chen Yung-Liang Wan Yau-Yau Wai Ho-Ling Liu 《Journal of digital imaging》2004,17(4):279-284
Clinical magnetic resonance imaging (MRI) scanners play an important role in the diagnosis of diseases and management of patient treatment. Quality assurance (QA) of the clinical MRI scanners is mandatory to obtain optimal images in a modern hospital. In this report, the phantom test for the American College of Radiology (ACR) MRI accreditation is used as the essential part of the MRI QA protocols. Seven important assessments of MR image quality are included as follows: geometric accuracy, high-contrast resolution, slice thickness accuracy, slice position accuracy, image intensity uniformity, percent signal ghosting, and low-contrast object detectability. In addition, signal-to-noise ratio and central frequency are monitored as well. The MRI QA procedures were applied to four clinical MRI scanners in our institute twice within 3 months. According to the QA results, the service engineers were more efficient in solving scanners problems when the ACR phantom test was run. 相似文献
88.
89.
人TH基因重组腺病毒的构建及生物学活性研究 总被引:2,自引:0,他引:2
将人酪氨酸羟化酶cDNA表达盒克隆于质粒型腺病毒载体p△Elsp1A,得到重组质粒pAd-TH。随后用脂质体法将重组质粒pAd-TH和拯救型腺病毒质粒pBHG11一起共转染293细胞,通过体内同源重组生成重组腺病毒AdCMVth,THcDNA重组进入腺病毒E1区并受CMV启动子控制。采用形态学、病毒核酸酶切和PCR/RT-PCR等方法进行鉴定正确。重组腺病毒滴度达到1010pfu/ml。初步结果表明,该重组腺病毒感染MN9D细胞后可使细胞内多巴胺水平增加1倍,显示出明显的TH生物学活性。提示TH重组腺病毒AdCMVth可作为高效的基因转移载体用于帕金森氏病基因治疗。 相似文献
90.
以21例Ⅱ期高血压患者、21例Ⅱ期高血压病高胰岛素血症患者及20例正常人为研究对象,以全血比粘度、全血还原比粘度、血浆比粘度、红细胞压积及血浆甘油三酯、总胆固醇、高密度脂蛋白为指标;结果表明Ⅱ期高血压病患者全血比粘度、全血还原比粘度较正常人高,Ⅱ期高血压病高胰岛素血症患者亦较单纯高血压病患者进一步增高,同时其血浆甘油三酯较单纯高血压病患者增高,高密度脂蛋白降低.而血浆比粘度、红细胞压积、总胆固醇三组间无显著性差异。单纯高血压病患者与正常人组比较血脂无差异。因而认为高血压病患者的高胰岛素血症可使高血压病患者增高的血粘度进一步增高,且血粘度的增高主要是红细胞机能、代谢的改变所致。单纯高血压病患者血脂改变不明显,高血压病患者血脂的改变主要是由高胰岛素血症所致。 相似文献