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11.
12.
Dobrovolny R Dvorakova L Ledvinova J Magage S Bultas J Lubanda JC Elleder M Karetova D Pavlikova M Hrebicek M 《Journal of molecular medicine (Berlin, Germany)》2005,83(8):647-654
We have identified 21 different -galactosidase A gene (GLA) mutations in 22 unrelated Czech and Slovak families with Fabry disease. Eleven of these mutations were novel (point mutations D93N, A135V, D155H, G171R, Q280K, G360S, Q330X, splicing errors c.194ins14, c.801ins36 and deletions c.674_732del59, g.3405_6021del2617). Genotyping of family members for family-specific mutations revealed 55 heterozygotes that manifested clinical symptoms of different severity. To examine the contribution of X-inactivation skewing to disease manifestation in Fabry heterozygotes, we have adopted the Mainz severity scoring scheme and compared the score values with the X-inactivation status in 39 carriers in an age-dependent manner. The age-score trendline of Fabry females who had a predominantly inactivated X-chromosome bearing a wild-type GLA allele (10 of 38 females) was markedly steeper than in the rest of the cohort. One female carrier with an inactivated mutated allele had a low score value when compared to the other heterozygotes of the same age. These data suggest that X-inactivation is indeed a major factor determining the severity of clinical involvement in Fabry heterozygotes. There was a statistically significant difference between the severity score values of heterozygotes with random and non-random X-chromosome inactivation at the 5% level of significance. Further studies will show if the degree of the wildtype allele inactivation will be useful as a predictive marker of severity of phenotype in Fabry heterozygotes. Although the correlation between X-inactivation skewing and presentation of the disease in Fabry heterozygotes has previously been suggested in the literature, this report is among the first attempts to examine this relationship systematically. 相似文献
13.
Davide Serrano Chiara Pozzi Silvia Guglietta Bruno Fosso Mariano Suppa Patrizia Gnagnarella Federica Corso Federica Bellerba Debora Macis Valentina Aristarco Paolo Manghi Nicola Segata Cristina Trovato Maria Giulia Zampino Marinella Marzano Bernardo Bonanni Maria Rescigno Sara Gandini 《Nutrients》2021,13(2)
Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process. 相似文献
14.
Charles Varnell Jr Lyndsay A. Harshman Laurie Smith Chunyan Liu Shiran Chen Samhar Al-Akash Gina-Marie Barletta Craig Belsha Paul Brakeman Abanti Chaudhuri Paul Fadakar Rouba Garro Caroline Gluck Jens Goebel David Kershaw Debora Matossian Corina Nailescu Hiren P. Patel Cozumel Pruette Saritha Ranabothu Nancy Rodig Jodi Smith Judith Sebestyen VanSickle Patricia Weng Lara Danziger-Isakov David K. Hooper Michael Seifert 《American journal of transplantation》2021,21(8):2740-2748
There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes. 相似文献
15.
Hiram Larangeira de Almeida Jr Debora Sarzi Sartori Janaína Kopp Carolina Dahmer Velloso Valeria Magalh?es Jorge 《Anais brasileiros de dermatologia》2013,88(4):620-622
Hydroa Vaciniforme is a very rare photodermatosis that is mainly seen in childhood.
An 18 year old female student reported that since the age of 5 she has been suffering
necrotic lesions and vesicles lesions in exposed areas, leaving asymptomatic
varioliform scars, which worsened in summer. Light microscopy showed epidermal
necrosis with lymphocytic infiltration. Sunscreens were prescribed with light
improvement. 相似文献
16.
Donna Achmadi Debora M. Kagohara Larah van der Meer Mark F. O’Reilly Giulio E. Lancioni Dean Sutherland Russell Lang Peter B. Marschik Vanessa A. Green Jeff Sigafoos 《Research in autism spectrum disorders》2012,6(4):1258-1264
We evaluated a program for teaching two adolescents with autism spectrum disorders (ASD) to perform more advanced operations on an iPod-based speech-generating device (SGD). The effects of the teaching program were evaluated in a multiprobe multiple baseline across participants design that included two intervention phases. The first intervention focused on teaching the students to navigate between two screen pages and complete a multi-step response sequence to request preferred stimuli. The second intervention aimed to teach the students to turn on and unlock the device prior to navigating to the correct screen pages. Teaching procedures included response prompting, prompt fading, and differential reinforcement. Results showed that both interventions were effective in teaching the respective operations. Learning advanced operation of the iPod-based SGD could be seen as one way to promote greater independence in using such devices for multi-step communication. 相似文献
17.
Debora M. Miranda Bernardo L. Wajchenberg† Maria R. Calsolari‡ Marcos J. Aguiar José M. C. L. Silva§ Marcia G. Ribeiro¶ Cristina Fonseca¶ Daniela Amaral¶ Wolfanga L. Boson Bruna A. Resende Luiz De Marco 《Clinical endocrinology》2009,71(4):512-517
Context Congenital generalized lipodystrophy, or Berardinelli–Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present.
Design We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.
Results Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518–519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A).
Conclusions We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli–Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome). 相似文献
Design We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.
Results Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518–519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A).
Conclusions We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli–Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome). 相似文献
18.
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene 总被引:7,自引:0,他引:7 下载免费PDF全文
Borrello MG Alberti L Fischer A Degl'innocenti D Ferrario C Gariboldi M Marchesi F Allavena P Greco A Collini P Pilotti S Cassinelli G Bressan P Fugazzola L Mantovani A Pierotti MA 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(41):14825-14830
Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes (CCL20, CCL2, CXCL8, CXCR4, L-selectin, GM-CSF, IL1B, MMP9, UPA, and SPP1/OPN) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET/PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET/PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior. 相似文献
19.
Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor 总被引:1,自引:0,他引:1 下载免费PDF全文
Vannini A Volpari C Filocamo G Casavola EC Brunetti M Renzoni D Chakravarty P Paolini C De Francesco R Gallinari P Steinkühler C Di Marco S 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(42):15064-15069
Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents. 相似文献
20.
de Lima Silva Alvaro Henrique Bernardo Radulski Debora Rasec Pereira Gabriela Saidel Acco Alexandra Zanoveli Janaina Menezes 《Metabolic brain disease》2022,37(4):1095-1110
Metabolic Brain Disease - Anxiety Disorders and Posttraumatic Stress Disorders (PTSD) associated with type-1 diabetes mellitus (T1DM) are increasingly common comorbidities and the treatment is... 相似文献