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991.
Jacek Pilch Agnieszka A. Koppolu Anna Walczak Victor A. Murcia Pienkowski Anna Biernacka Paweł Skiba Joanna Machnik‐Broncel Piotr Gasperowicz Joanna Kosińska Małgorzata Rydzanicz Ewa Emich‐Widera Rafał Płoski 《Clinical genetics》2018,94(3-4):381-385
The HNRNPH2‐associated disease (mental retardation, X‐linked, syndromic, Bain type [MRXSB, MIM #300986]) is caused by de novo mutations in the X‐linked HNRNPH2 gene. MRXSB has been described in six female patients with dysmorphy, developmental delay, intellectual disability, autism, hypotonia and seizures. The reported HNRNPH2 mutations were clustered in the small domain encoding nuclear localization signal; in particular, the p.Arg206Trp was found in four independent de novo events. HNRNPH1 is a conserved autosomal paralogue of HNRNPH2 with a similar function in regulation of pre‐mRNAs splicing but so far it has not been associated with human disease. We describe a boy with a disease similar to MRXSB in whom a novel de novo mutation c.616C>T (p.Arg206Trp) in HNRNPH1 was found (ie, the exact paralogue of the recurrent HNRNPH2 mutation). We propose that defective function of HNRNPH2 and HNRNPH1 nuclear localization signal has similar clinical consequences. An important difference between the two diseases is that the HNRNPH1‐associated syndrome may occur in boys (as in the case of our proband) which is well explained by the autosomal (chr5q35.3) rather than X‐linked localization of the HNRNPH2 gene. 相似文献
992.
Aleksander W. Demiaszkiewicz Anna M. Pyziel Izabela Kuligowska Jacek Lachowicz 《Acta parasitologica / Witold Stefański Institute of Parasitology, Warszawa, Poland》2014,59(4):758-762
Angiostrongylus vasorum belongs to the superfamily of Metastrongyloidea. This nematode occurs in foxes, dogs and other predators. The Nematode A. vasorum place themselves in the pulmonary artery and its branches, and in the right ventricle and atrium of the heart. Numerous species of land snails are the intermediate hosts of the parasite. In 2013, lungs and hearts of 76 foxes shot in the Forest District G??boki Bród in Augustowska Primeval Forest were parasitologically necropsied. Four of the examined foxes were infected with the nematode A. vasorum, a prevalence of 5.2%. In one fox pericardium there were 6 male and 6 female nematodes. In the remaining three foxes nematodes were localized in the pulmonary artery. In two foxes 2 specimens of nematodes were detected (male and female, and two females) while 1 female was detected in the other fox. This is the first report of the presence of the nematode A. vasorum in fox in Poland. 相似文献
993.
994.
Dhaarini Murugan Michael H. Albert Jörg Langemeier Jens Bohne Jacek Puchalka Päivi M. Järvinen Fabian Hauck Anne K. Klenk Christine Prell Stephanie Schatz Jana Diestelhorst Barbara Sciskala Naschla Kohistani Bernd H. Belohradsky Susanna Müller Thomas Kirchner Mark R. Walter Philip Bufler Aleixo M. Muise Scott B. Snapper Sibylle Koletzko Christoph Klein Daniel Kotlarz 《Journal of clinical immunology》2014,34(3):331-339
Purpose
Loss-of-function mutations in IL10 and IL10R cause very early onset inflammatory bowel disease (VEO-IBD). Here, we investigated the molecular pathomechanism of a novel intronic IL10RA mutation and describe a new therapeutic approach of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT).Methods
Clinical data were collected by chart review. Genotypes of IL10 and IL10R genes were determined by Sanger sequencing. Expression and function of mutated IL-10R1 were assessed by quantitative PCR, Western blot analysis, enzyme-linked immunosorbent assays, confocal microscopy, and flow cytometry.Results
We identified a novel homozygous point mutation in intron 3 of the IL10RA (c.368-10C > G) in three related children with VEO-IBD. Bioinformatical analysis predicted an additional 3′ splice site created by the mutation. Quantitative PCR analysis showed normal mRNA expression of mutated IL10RA. Sequencing of the patient’s cDNA revealed an insertion of the last nine nucleotides of intron 3 as a result of aberrant splicing. Structure-based modeling suggested misfolding of mutated IL-10R1. Western blot analysis demonstrated a different N-linked glycosylation pattern of mutated protein. Immunofluorescence and FACS analysis revealed impaired expression of mutated IL-10R1 at the plasma membrane. In the absence of HLA-identical donors, T cell replete haploidentical HSCT was successfully performed in two patients.Conclusions
Our findings expand the spectrum of IL10R mutations in VEO-IBD and emphasize the need for genetic diagnosis of mutations in conserved non-coding sequences of candidate genes. Transplantation of haploidentical stem cells represents a curative therapy in IL-10R-deficient patients, but may be complicated by non-engraftment. 相似文献995.
Wojciech Jelski Miroslaw Kozlowski Jerzy Laudanski Jacek Niklinski Maciej Szmitkowski 《Clinical and experimental medicine》2009,9(2):131-137
Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the human esophageal mucosa. In
our last experiments we have shown that ADH and ALDH are present also in the esophageal cancer cells. Moreover, the activities
of total ADH and class IV isoenzymes were significantly higher in cancer tissue than in healthy mucosa, which suggests that
these changes may be reflected by enzyme activity in the serum. Therefore, we measured the activity of total alcohol dehydrogenase,
and classes I–IV of this enzyme and aldehyde dehydrogenase in the sera of patients with this cancer. Serum samples were taken
for routine biochemical investigation from 67 patients with esophageal cancer before treatment. Total ADH activity was measured
by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde
as a substrate. For the measurement of the activity of class I and II isoenzymes, we employed the fluorometric methods, with
class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was measured by the photometric method
with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. A statistically significant increase of class IV alcohol dehydrogenase isoenzymes was found
in the sera of cancer patients. The median activity of this class isoenzyme in the total cancer group increased by about 26.5%
(7.42 mU/l) in comparison to the control level (5.46 mU/l). The total alcohol dehydrogenase activity was significantly higher
(30%) among patients with cancer. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The activity
of the class I ADH isoenzyme was significantly higher in the sera of drinkers with esophageal cancer than non-drinking patients.
The increased total activity of alcohol dehydrogenase and class IV isoenzyme in the sera of patients with esophageal cancer
probably can be caused by release of this isoenzyme from cancer cells or might be stimulated by alcohol drinking. 相似文献
996.
Krystyna Galazka Lukasz Wicherek Kazimierz Pitynski Jacek Kijowski Kszysztof Zajac Wieslawa Bednarek Magdalena Dutsch‐Wicherek Krzysztof Rytlewski Jaroslaw Kalinka Antoni Basta Marcin Majka 《American journal of reproductive immunology (New York, N.Y. : 1989)》2009,61(2):136-146
Problem The initiation of labor is accompanied by alterations in the level of maternal immune tolerance toward fetal antigens. It is a complex molecular response leading to a brief activation of the maternal immune system with an accompanying capacity to restrict this same activation. The aim of our study was to evaluate the subpopulation of regulatory T cells (Tregs) and B7‐H4 macrophages in the decidua basalis during cesarean sections performed on patients in various stages of labor. Method of study The decidual tissue samples evaluated in our study were obtained from 23 pregnant women who underwent cesarean sections at term. Moreover, the patients were divided into three subgroups according to the progression of labor at the time of the cesarean. The presence of Treg cells and B7‐H4 positive macrophages were analysed by fluorescence‐activated cell sorter. Results The percentages of FOXP3+ cells in the subpopulation of CD25+ CD4+ T lymphocytes found in the deciduas of patients decreased with the successive stages of labor, while the percentages of B7‐H4 positive cells in the macrophage subpopulation remained almost constant. Conclusion These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7‐H4+ macrophages that enable the restriction of this same activation as labor progresses. 相似文献
997.
Oldak M Majewski S Grzela T Stark S Malejczyk M Osiecka-Iwan A Fuchs PG Jablonska S Pfister HJ Malejczyk J 《International journal of molecular medicine》2004,13(1):187-191
The aim of the present study was to characterise natural cell-mediated cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1 DNA sequences cloned in sense and antisense orientation and to evaluate their lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia verruciformis (EV), a rare disease associated with life-long infection by specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells. Analysis of NK cell cytotoxic activity against different COS cell lines has revealed that lymphocytes from healthy subjects killed COS-L1S cells significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly more efficient lysis of COS-L1S cells was also observed in EV patients. Thus, expression of HPV L1 renders target cells more susceptible to NK-mediated cytotoxicity that may enable more effective elimination of transformed cells. 相似文献
998.
Alicja Nowak Jacek P. Szaflik Mira Gacek Karolina Przybylowska-Sygut Anna Kamińska Jerzy Szaflik Ireneusz Majsterek 《Archives of Medical Science》2014,10(6):1206-1213
Introduction
Glaucoma is a neurodegenerative disease that is often associated with high intraocular pressure (IOP). One of the effects of elevated IOP is disorder of neurotrophic molecules transport, including brain-derived neurotrophic factor (BDNF) and recruit specific cellular proteins called “heat shock proteins” (HSPs). The aim of this study was to evaluate a relationship between the BDNF and HSP70-1 gene polymorphisms with risk occurrence of primary open-angle glaucoma (POAG).Material and methods
The study consisted of 167 patients with POAG (mean age: 73 ±9) and 193 healthy subjects (mean age: 64 ±13). Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP, using the following restriction enzymes: NlaIII (rs6265) and BsrBI (rs1043618). The Heidelberg retinal tomography (HRT) clinical parameters were also analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated.Results
Comparison of the distributions of genotypes and alleles of the 196G/A polymorphism of the BDNF gene as well as 190G/C polymorphism of the HSP70-1 gene and analysis of the odds ratio (OR) showed no statistically significant differences between POAG patients and controls (p > 0.05). However, there was a statistically significant association of the 196G/A of BDNF and 190G/C of HSP70-1 gene polymorphisms with progression of POAG depending on values of clinical parameters. 196G/A of BDNF correlated with the parameters GDx and RA (p = 0.03; p = 0.002, respectively), while 190G/C of HSP70-1 correlated with c/d and RA (p = 0.014, p = 0.024, respectively).Conclusions
The BDNF 196G/A and HSP70-1 190G/C gene polymorphisms may be related to progression of POAG. 相似文献999.
Katarzyna Sznurkowska Anton Żawrocki Jacek Sznurkowski Maciej Zieliński Piotr Landowski Katarzyna Plata-Nazar 《Immunological investigations》2016,45(8):787-796
ABSTRACTBackground/Aims: To determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+ cells) in peripheral blood and the number of FOXP3+ cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease.Material and methods: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn’s disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively. The disease activity was assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn’s Disease Activity Index (PCDAI). Quantification of regulatory T cells of CD4+CD25highFOXP3+ phenotype in peripheral blood was based on three-color flow cytometry. Mucosal Tregs represented by FOXP3+ cells were evaluated using immunohistochemistry.Results: Median proportion of CD4+CD25highFOXP3+ cells among CD4+ T cells in peripheral blood (5.1%, range 1.7–84% vs. 4.3%, range 2–8.1%, p = 0.023) and median number of intestinal FOXP3+ cells (115.33 per high-power field, hpf, range 39.33–375.67 vs. 10.16 per hpf, range 5–30, p = 0.0001) were significantly higher in children with IBD than in the controls. The proportion of circulating Tregs and the number of intestinal FOXP3+ cells did not correlate with clinical activity of the disease, as well as with endoscopic and histopathologic scoring. No significant correlation was found between the percentage of peripheral CD4+CD25highFOXP3+ cells and the number of intestinal FOXP3+cells.Conclusions: Children with IBD likely do not present with a quantitative deficiency of circulating and intestinal Tregs at the moment of diagnosis. 相似文献
1000.
Jacek Zieliński Rados?aw Jaworski Ninela Irga Janusz Wies?aw Kruszewski Janusz Jaskiewicz 《Archives of Medical Science》2013,9(1):86-92