首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2663篇
  免费   188篇
  国内免费   21篇
耳鼻咽喉   62篇
儿科学   144篇
妇产科学   122篇
基础医学   237篇
口腔科学   132篇
临床医学   270篇
内科学   421篇
皮肤病学   241篇
神经病学   176篇
特种医学   121篇
外科学   409篇
综合类   41篇
一般理论   2篇
预防医学   114篇
眼科学   108篇
药学   119篇
中国医学   27篇
肿瘤学   126篇
  2023年   27篇
  2022年   29篇
  2021年   73篇
  2020年   52篇
  2019年   88篇
  2018年   101篇
  2017年   89篇
  2016年   86篇
  2015年   101篇
  2014年   113篇
  2013年   154篇
  2012年   191篇
  2011年   235篇
  2010年   111篇
  2009年   71篇
  2008年   140篇
  2007年   180篇
  2006年   137篇
  2005年   154篇
  2004年   136篇
  2003年   110篇
  2002年   125篇
  2001年   71篇
  2000年   65篇
  1999年   48篇
  1998年   23篇
  1997年   14篇
  1996年   13篇
  1995年   6篇
  1994年   5篇
  1993年   3篇
  1992年   13篇
  1991年   20篇
  1990年   7篇
  1989年   7篇
  1988年   9篇
  1987年   5篇
  1986年   12篇
  1985年   5篇
  1984年   4篇
  1982年   3篇
  1979年   5篇
  1977年   3篇
  1975年   2篇
  1973年   3篇
  1971年   2篇
  1970年   4篇
  1969年   3篇
  1968年   3篇
  1966年   4篇
排序方式: 共有2872条查询结果,搜索用时 15 毫秒
91.
Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV‐16), which is most common worldwide, and HPV‐52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV‐16 or HPV‐52. Samples were amplified further for their E6/E7 genes using type‐specific primers and analyzed genetically. Seventy‐nine HPV‐16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African‐2. The prevalences of HPV‐16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV‐52 E6/E7 genes analyzed successfully were grouped into four lineages, A–D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV‐16 and HPV‐52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV‐16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV‐16 and HPV‐52 E6/E7 genes can be a useful molecular‐epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069–1076, 2013. © 2013 Wiley Periodicals, Inc.  相似文献   
92.

OBJECTIVES:

Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin.

METHOD:

Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers.

RESULTS:

We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population.

CONCLUSION:

Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.  相似文献   
93.
94.
Introduction and Aim: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). Materials and Methods: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. Results: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log10 reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. Conclusion: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.  相似文献   
95.
In recent years, familial pheochromocytoma (PHEO) with germline mutations in the MAX (MYC associated factor X) gene has been reported in a few cases. Here, we investigated a 25–year-old patient with multiple PHEOs associated with a non-sense germline MAX mutation. Preoperative 18F-FDOPA PET/CT revealed bilateral adrenal involvement with multiple tumors. In addition, both adrenal glands were found to have diffuse or nodular adrenal medullary hyperplasia (AMH), a histopathological feature previously described as a precursor of MEN2- and SDHB-related PHEOs but not MAX. After bilateral adrenalectomy, different paraffin-embedded and frozen samples were analyzed for allelic imbalances of the MAX gene using allelic quantification by pyrosequencing. The expression of the protein MAX was studied by immunohistochemistry. All PHEOs but also nodular AMH exhibited a loss of the normal allele. By contrast, the diffuse AMH did not show loss-of-heterozygosity. Nevertheless, immunohistochemistry demonstrated loss of protein MAX expression in all samples including diffuse hyperplasia, suggesting a causative role of MAX mutation for both PHEOs and AMH. The present case shows that both nodular and diffuse AMH belongs to the spectrum of MAX-related disease. These data support the possible continuum between nodular AMH and PHEO, expanding the qualification of micro-PHEO to nodular AMH.  相似文献   
96.
Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms.  相似文献   
97.
98.
IntroductionSome improvements have been developed with new generations of nickel-titanium (NiTi) rotary instruments that led to their successful and extensive application in clinical practice. The purpose of this in vitro study was to compare the root canal preparations performed by using GT Series X and Twisted File systems produced by innovative manufacturing process with Revo-S, RaCe, Mtwo, and ProTaper Universal systems manufactured directly from conventional nitinol and with stainless steel K-Flexofile instruments.MethodsThe mesiobuccal root canals of 140 maxillary first permanent molars that had between 30°–40° curvature angle and 4- to 9-mm curvature radius of the root canal were used. After root canal preparations made by using GT Series X, Twisted File, Revo-S, RaCe, Mtwo, and ProTaper Universal NiTi rotary systems and stainless steel K-Flexofile instruments, transportation occurred in the root canal, and alteration of working length (WL) was assessed by using a modified double-digital radiographic technique. The data were compared by the post hoc Tukey honestly significant difference test.ResultsNiTi rotary systems caused less canal transportation and alteration of WL than K-Flexofile instruments (P < .05). There was no significant difference between NiTi rotary system groups at any levels (P > .05) except 2.5 mm from the WL. At this level ProTaper Universal system caused significant canal transportation (P < .05).ConclusionsGT Series X and Twisted File rotary systems produced with innovative process were concluded to shape the curved canals to result in minimal canal transportation, similar to Revo-S, RaCe, Mtwo, and ProTaper Universal rotary systems manufactured by traditional methods.  相似文献   
99.
Chronic pain is a major health care issue characterized by ongoing pain and a variety of sensory, cognitive, and affective abnormalities. The neural basis of chronic pain is still not completely understood. Previous work has implicated prefrontal brain areas in chronic pain. Furthermore, prefrontal neuronal oscillations at gamma frequencies (60–90 Hz) have been shown to reflect the perceived intensity of longer lasting experimental pain in healthy human participants. In contrast, noxious stimulus intensity has been related to alpha (8–13 Hz) and beta (14–29 Hz) oscillations in sensorimotor areas. However, it is not fully understood how the intensity of ongoing pain as the key symptom of chronic pain is represented in the human brain. Here, we asked 31 chronic back pain patients to continuously rate their ongoing pain while simultaneously recording electroencephalography (EEG). Time–frequency analyses revealed a positive association between ongoing pain intensity and prefrontal beta and gamma oscillations. No association was found between pain and alpha or beta oscillations in sensorimotor areas. These findings indicate that ongoing pain as the key symptom of chronic pain is reflected by neuronal oscillations implicated in the subjective perception of longer lasting pain rather than by neuronal oscillations related to the processing of objective nociceptive input. The findings, thus, support a dissociation of pain intensity from nociceptive processing in chronic back pain patients. Furthermore, although possible confounds by muscle activity have to be taken into account, they might be useful for defining a neurophysiological marker of ongoing pain in the human brain.  相似文献   
100.
Aim To compare the efficacy of conventional and new retreatment instruments when removing gutta‐percha root fillings in curved root canals. Methodology A total of 56 curved molar roots were instrumented with ProFile instruments and filled using system B and Obtura II. The root fillings were removed with manual K‐files and Hedström files (Dentsply Maillefer), ProFile (Dentsply Maillefer), R‐Endo (Micro–Mega) or ProTaper Universal retreatment files (Dentsply Maillefer). Eucalyptol was used as a solvent with all techniques. Bucco‐lingual and proximal radiographs of the roots were exposed and the percentage area of the remaining material was calculated by dividing the area of remaining filling material by the area of canal wall. Data were statistically analysed with Kruskal–Wallis and Mann–Whitney U tests (P = 0.05). Results None of the techniques completely removed the root filling materials. No significant differences were found amongst the coronal, middle and apical thirds in both radiographic projections (P > 0.05). In the bucco‐lingual direction, the remaining filling material was significantly less following manual instrumentation than R‐Endo and ProTaper instrumentation (P < 0.05). In the proximal view, it was significantly less following manual and ProFile instrumentation than R‐Endo (P < 0.05). Complete removal of filling material occurred only in three specimens (with manual instruments). Manual instruments were significantly faster than R‐Endo and ProFile (P < 0.05). More procedural errors (five fractured instruments and two perforation) were noted when using ProTaper (P < 0.05). Conclusions In this laboratory study in curved molar roots, ProTaper Retreatment and R‐Endo instruments were less effective in removing filling material from canal walls than manual and ProFile instruments.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号