全文获取类型
收费全文 | 8167篇 |
免费 | 472篇 |
国内免费 | 35篇 |
专业分类
耳鼻咽喉 | 68篇 |
儿科学 | 284篇 |
妇产科学 | 194篇 |
基础医学 | 1250篇 |
口腔科学 | 173篇 |
临床医学 | 719篇 |
内科学 | 1686篇 |
皮肤病学 | 246篇 |
神经病学 | 865篇 |
特种医学 | 167篇 |
外科学 | 626篇 |
综合类 | 67篇 |
一般理论 | 3篇 |
预防医学 | 668篇 |
眼科学 | 185篇 |
药学 | 770篇 |
中国医学 | 11篇 |
肿瘤学 | 692篇 |
出版年
2024年 | 8篇 |
2023年 | 65篇 |
2022年 | 215篇 |
2021年 | 350篇 |
2020年 | 204篇 |
2019年 | 217篇 |
2018年 | 281篇 |
2017年 | 195篇 |
2016年 | 278篇 |
2015年 | 274篇 |
2014年 | 318篇 |
2013年 | 462篇 |
2012年 | 690篇 |
2011年 | 669篇 |
2010年 | 352篇 |
2009年 | 301篇 |
2008年 | 481篇 |
2007年 | 525篇 |
2006年 | 500篇 |
2005年 | 460篇 |
2004年 | 483篇 |
2003年 | 410篇 |
2002年 | 383篇 |
2001年 | 53篇 |
2000年 | 48篇 |
1999年 | 45篇 |
1998年 | 50篇 |
1997年 | 51篇 |
1996年 | 40篇 |
1995年 | 23篇 |
1994年 | 26篇 |
1993年 | 22篇 |
1992年 | 17篇 |
1991年 | 17篇 |
1990年 | 10篇 |
1989年 | 17篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
排序方式: 共有8674条查询结果,搜索用时 15 毫秒
121.
Anil Rana Jimi Marin Alex Monika Chauhan Gaurav Joshi Raj Kumar 《Medicinal chemistry research》2015,24(3):903-920
Past few decades have witnessed the dawn of new diseases in which cancer is a major problem and the race ensued to eradicate cancer by charting out various effective therapeutic regimens. Circumventing resistance issues and combating the toxicity and selectivity problems are matter-of-concern in cancer treatment. Persistent failure to ensure complete remission and eradication of cancer instigated the researchers to exploit the strategies of combining pharmacophores as targeted therapeutic agents. Momentous improvement in the pharmacokinetic as well as pharmacodynamic profile resulting in the enhancement of bioavailability was seen with the introduction of these pharmacophores. The scope of molecular hybridization can be clearly exemplified through the US-FDA approved estramustine and others such as CUDC-101, CBLC-137, PLX3397, E-3810, and CUDC-907 that are currently in different phases of clinical trials. This review seeks to highlight and discuss anti-proliferative activity of some important hybrid, dual, and multi-targeted pharmacophores reported to date along with their designs, structure activity relationships, scope, and limitations. Further, an emphasis has been made to summarize US-FDA approved as well as drugs currently undergoing clinical trials of anticancer drug development. 相似文献
122.
123.
Udo Rüb Kay Seidel Jean Paul Vonsattel Herwig W. Lange Wolfgang Eisenmenger Monika Götz Domenico Del Turco Mohamed Bouzrou Horst‐Werner Korf Helmut Heinsen 《Brain pathology (Zurich, Switzerland)》2015,25(6):701-711
Huntington's disease (HD), an autosomal dominantly inherited polyglutamine or CAG repeat disease along with somatomotor, oculomotor, psychiatric and cognitive symptoms, presents clinically with impairments of elementary and complex visual functions as well as altered visual‐evoked potentials (VEPs). Previous volumetric and pathoanatomical post‐mortem investigations pointed to an involvement of Brodmann's primary visual area 17 (BA17) in HD. Because the involvement of BA17 could be interpreted as an early onset brain neurodegeneration, we further characterized this potential primary cortical site of HD‐related neurodegeneration neuropathologically and performed an unbiased estimation of the absolute nerve cell number in thick gallocyanin‐stained frontoparallel tissue sections through the striate area of seven control individuals and seven HD patients using Cavalieri's principle for volume and the optical disector for nerve and glial cell density estimations. This investigation showed a reduction of the estimated absolute nerve cell number of BA17 in the HD patients (71 044 037 ± 12 740 515 nerve cells) of 32% in comparison with the control individuals (104 075 067 ± 9 424 491 nerve cells) (Mann–Whitney U‐test; P < 0.001). Additional pathoanatomical studies showed that nerve cell loss was most prominent in the outer pyramidal layer III, the inner granular layers IVa and IVc as well as in the multiform layer VI of BA17 of the HD patients. Our neuropathological results in BA17 confirm and extend previous post‐mortem, biochemical and in vivo neuroradiological HD findings and offer suitable explanations for the elementary and complex visual dysfunctions, as well as for the altered VEP observed in HD patients. 相似文献
124.
Monika Oláhová Tobias B Haack Charlotte L Alston Jessica AC Houghton Langping He Andrew AM Morris Garry K Brown Robert McFarland Zofia MA Chrzanowska-Lightowlers Robert N Lightowlers Holger Prokisch Robert W Taylor 《European journal of human genetics : EJHG》2015,23(7):935-939
Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene. 相似文献
125.
Susanna?Nikolaus Georg?H.?Waetzig Sven?Butzin Monika?Ziolkiewicz Natalie?Al-Massad Florian?Thieme Ulf?L?vgren Birgitte?B.?Rasmussen Torsten?M.?Reinheimer Dirk?Seegert Philip?Rosenstiel Silke?Szymczak Stefan?SchreiberEmail authorView authors OrcID profile 《International journal of colorectal disease》2018,33(7):927-936
Purpose
Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).Methods
Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.Results
IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.Conclusions
Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.126.
11p15 duplication and 13q34 deletion with Beckwith–Wiedemann syndrome and factor VII deficiency
下载免费PDF全文
![点击此处可从《Pediatrics international》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dorota Jurkiewicz Monika Kugaudo Anna Tańska Angelika Wawrzkiewicz‐Witkowska Agnieszka Tomaszewska Marzena Kucharczyk Agata Cieślikowska Elżbieta Ciara Małgorzata Krajewska‐Walasek 《Pediatrics international》2015,57(3):486-491
Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith–Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation‐sensitive multiplex ligation‐dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. 相似文献
127.
Favorable four‐yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation‐associated HUS
下载免费PDF全文
![点击此处可从《Pediatric transplantation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ryszard Grenda Wioletta Jarmużek Jacek Rubik Sylwester Prokurat Monika Miklaszewska Dorota Drozdz Katarzyna Zachwieja Gianluigi Ardissino Johannes Hofer 《Pediatric transplantation》2015,19(6):E130-E134
aHUS is a clinical challenge for successful renal transplantation. Case report: A 14‐yr‐old girl lost her kidneys at the age of 7, due to CFH antibodies and CFH‐related protein (CFHR1/CFHR3) homozygous deletion‐associated aHUS. CFH, CFI, and MCP gene mutations were excluded. The patient was a candidate for renal transplantation despite persistent presence of CFH antibodies (up to 539 AU/mL). Treatment with MMF, IVIG, and repeated PF (n = 8) was introduced while being placed on urgent waiting list. Three years after aHUS onset, the patient underwent the deceased donor renal transplantation “under cover” of PF, as PF was performed directly prior to surgery and, then, PFs were repeated up to overall 14 sessions. Quadruple immunosuppression (basiliximab + tacrolimus + MMF + prednisolone) was used. Moderate symptoms of aHUS (hemolysis, low platelets, and low C3) were present within first seven days post‐transplant and then normalized with PF therapy. The patient remained stable during four yr of further follow‐up after transplantation. Conclusion: Specific pre‐ and post‐transplant management allowed successful renal transplantation in a CFH antibody‐positive patient. 相似文献
128.
129.
The PCBP1 gene encoding poly(rc) binding protein i is recurrently mutated in Burkitt lymphoma
下载免费PDF全文
![点击此处可从《Genes, chromosomes & cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rabea Wagener Sietse M. Aukema Matthias Schlesner Andrea Haake Birgit Burkhardt Alexander Claviez Hans G. Drexler Michael Hummel Markus Kreuz Markus Loeffler Maciej Rosolowski Cristina Lpez Peter Mller Julia Richter Marius Rohde Matthew J. Betts Robert B. Russell Stephan H. Bernhart Steve Hoffmann Philip Rosenstiel Markus Schilhabel Monika Szczepanowski Lorenz Trümper Wolfram Klapper Reiner Siebert 《Genes, chromosomes & cancer》2015,54(9):555-564
The genetic hallmark of Burkitt lymphoma is the translocation t(8;14)(q24;q32), or one of its light chain variants, resulting in IG‐MYC juxtaposition. However, these translocations alone are insufficient to drive lymphomagenesis, which requires additional genetic changes for malignant transformation. Recent studies of Burkitt lymphoma using next generation sequencing approaches have identified various recurrently mutated genes including ID3, TCF3, CCND3, and TP53. Here, by using similar approaches, we show that PCBP1 is a recurrently mutated gene in Burkitt lymphoma. By whole‐genome sequencing, we identified somatic mutations in PCBP1 in 3/17 (18%) Burkitt lymphomas. We confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11%) Burkitt lymphomas and in 6/16 (38%) Burkitt lymphoma cell lines. PCBP1 is an intron‐less gene encoding the 356 amino acid poly(rC) binding protein 1, which contains three K‐Homology (KH) domains and two nuclear localization signals. The mutations predominantly (10/12, 83%) affect the KH III domain, either by complete domain loss or amino acid changes. Thus, these changes are predicted to alter the various functions of PCBP1, including nuclear trafficking and pre‐mRNA splicing. Remarkably, all six primary Burkitt lymphomas with a PCBP1 mutation expressed MUM1/IRF4, which is otherwise detected in around 20–40% of Burkitt lymphomas. We conclude that PCBP1 mutations are recurrent in Burkitt lymphomas and might contribute, in cooperation with other mutations, to its pathogenesis. © 2015 Wiley Periodicals, Inc. 相似文献
130.