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101.
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene 总被引:7,自引:0,他引:7
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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
102.
103.
Emy Hiura Aline del Carmen Garcia Lopes Jeanne Saraiva da Paz Maylla Garschagen Gava Mayra Cunha Flecher Manuela Colares Filippe Elias de Freitas Soares Leandro Abreu da Fonseca Tracy Lacerda Jackson Victor de Araújo Fabio Ribeiro Braga 《Parasitology research》2015,114(9):3301-3308
The objective of this study was to evaluate the infectivity of Toxocara canis eggs after interacting with isolated nematophagous fungi of the species Duddingtonia flagrans (AC001) and Pochonia chlamydosporia (VC4), and test the predatory activity of the isolated AC001 on T. canis second stage larvae after 7 days of interaction. In assay A, 5000 embryonated T. canis eggs previously in contact with the AC001 and VC4 isolated for 10 days were inoculated into domestic chickens (Gallus gallus domesticus), and then these animals were necropsied to collect material (digested liver, intestine, muscles and lungs) at 3-, 7-, 14-, and 21-day intervals after inoculation. In assay A, the results demonstrated that the prior interaction of the eggs with isolated AC001 and VC4 decreases the amount of larvae found in the collected organs. Difference (p?<?0.01) was observed in the medium larvae counts recovered from liver, lung, intestine, and muscle of animals in the treated groups when compared to the animals in the control group. At the end of assay A, a percentage reduction of 87.1 % (AC001) and 84.5 % (VC4) respectively was recorded. In the result of assay B, the isolated AC001 showed differences (p?<?0.01) compared to the control group, with a reduction of 53.4 % in the recovery of L2. Through these results, it is justified to mention that prior interaction of embryonated T. canis eggs with the tested fungal isolates were efficient in reducing the development and migration of this parasite, in addition to the first report of proven predatory activity on L2. 相似文献
104.
Joana Vieira Carla Pinto Mariana Afonso Maria do Bom Sucesso Paula Lopes Manuela Pinheiro Isabel Veiga Rui Henrique Manuel R Teixeira 《European journal of human genetics : EJHG》2015,23(5):715-718
Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present β-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for β-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families. 相似文献
105.
Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism 总被引:6,自引:0,他引:6
Lanfranco F Gromoll J von Eckardstein S Herding EM Nieschlag E Simoni M 《European journal of endocrinology / European Federation of Endocrine Societies》2005,153(6):845-852
OBJECTIVE: To determine the frequency of mutations of the gonadotropin-releasing hormone receptor (GnRHR) and of the G protein-coupled receptor 54 (GPR54) genes in normosmic idiopathic hypogonadotropic hypogonadism (IHH). METHODS: In a retrospective study we analyzed the GnRHR and the GPR54 genes of 45 IHH patients and 50 controls. Genomic DNA was amplified by PCR to obtain partially overlapping amplicons encompassing the exon-intron boundaries of the GnRHR and GPR54 genes and analyzed by single-stranded conformation polymorphism gel electrophoresis and/or DNA sequencing. RESULTS: One heterozygous R262Q mutation of the GnRHR gene was identified in one patient with familial IHH. The silent single-nucleotide polymorphism (SNP) 453C > T occurred at the same frequency in patients and controls. One patient with sporadic IHH and consanguineous parents showed a novel homozygous sequence variation of the GPR54 gene (1001_1002insC) resulting in an open reading frame shift and elongation of 43 amino acids with an increased number of proline residues in the intracellular receptor domain. This patient had delayed puberty, low testosterone (3.4 nmol/l), and low-normal LH and FSH levels responsive to GnRH. Pulsatile GnRH administration normalized testosterone levels and induced spermatogenesis sufficiently to induce a pregnancy with assisted reproduction. Two common SNPs in exon 1 and exon 5 of the GPR54 gene showed similar frequency distribution and hormonal profiles in IHH and controls. CONCLUSIONS: Mutations of the GnRHR and of the GPR54 gene are rare in IHH and should be investigated especially in cases with autosomal recessive transmission. Common SNPs of the GnRHR and GPR54 genes do not play any role in IHH. 相似文献
106.
Jokubaitis VJ Sinka L Driessen R Whitty G Haylock DN Bertoncello I Smith I Péault B Tavian M Simmons PJ 《Blood》2008,111(8):4055-4063
Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map BB9 expression throughout hematopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and surrounding endothelial cells are BB9(+). Thereafter, BB9 is expressed by primitive hematopoietic cells in fetal liver and in umbilical cord blood (UCB). BB9(+)CD34(+) UCB cells transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice contribute 10-fold higher numbers of multilineage blood cells than their CD34(+)BB9(-) counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34(+) population. Protein microsequencing of the 160-kDa band corresponding to the BB9 protein established its identity as that of somatic angiotensin-converting enzyme (ACE). Although the role of ACE on human HSCs remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSCs throughout hematopoietic ontogeny and adulthood. 相似文献
107.
New insights into the pharmacokinetics of intravenous busulfan in children with sickle cell anemia undergoing bone marrow transplantation
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Javid Gaziev MD Antonella Isgrò MD Alessia Francesca Mozzi PhD Aurèlie Petain PhD Laurent Nguyen MD Cristiano Ialongo MD PhD Vincenzo Dinallo PhD Pietro Sodani MD Marco Marziali MD Marco Andreani PhD Manuela Testi PhD Katia Paciaroni MD Cristiano Gallucci MD Gioia De Angelis MD Cecilia Alfieri MD Michela Ribersani MD Guido Lucarelli MD 《Pediatric blood & cancer》2015,62(4):680-686
108.
Angeloni S Nicolini G Merli M Nicolao F Pinto G Aronne T Attili AF Riggio O 《The American journal of gastroenterology》2003,98(8):1844-1848
OBJECTIVES: Polymorphonuclear (PMN) cell count in ascitic fluid is the most useful test for the diagnosis of spontaneous bacterial peritonitis (SBP). We evaluated the validity of an automated blood cell counter for the PMN determination in ascitic fluid by comparing it with the traditional hematologic method with a light microscope in a manual counting chamber. METHODS: A total of 130 ascitic fluid samples were collected from 74 consecutive cirrhotics. The agreement between the two techniques was assessed according to Bland and Altman's method. The sensitivity, specificity, and positive and negative predictive values of the automated blood cell counter were calculated by considering the diagnosis of SBP as a PMN count > or = 250 cells/mm(3), determined by the manual method as the "gold standard." RESULTS: The mean PMN counts assessed by the manual method and the automated blood cell counter were 124 +/- 301 cells/mm(3) and 130 +/- 339 cells/mm(3), respectively (p = 0.89, ns). The mean +/- SD of the difference between manual and automated measurements was 6 +/- 61 cells/mm(3), whereas the limits of agreement were +127 cells/mm(3) (95% CI = +108 to +147) and -115 cells/mm(3) (95%CI = -96 to -135). SBP was diagnosed in 11 patients. All but one were correctly identified with the automated blood cell counter, with a sensitivity of 94% and a specificity of 100%; positive and negative predictive values were 100% and 99.1%, respectively. CONCLUSIONS: The manual method and the automated blood cell counter have a good agreement in the PMN determination in ascitic fluid, and the automated blood cell counter is a reliable tool for rapid diagnosis of SBP. 相似文献
109.
Fabianna Resende De Jesus-Moraleida Paulo Henrique Ferreira Manuela Loureiro Ferreira Juscelio Pereira Da Silva Marcella Guimarães Assis Leani Souza Máximo Pereira 《Revista brasileira de fisioterapia (S?o Carlos (S?o Paulo, Brazil))》2018,22(1):55-63
Objective
Low back pain (LBP) is little explored in the aging population especially when considering age-relevant and culturally dependent outcomes. We aimed to describe socio-demographic and clinical characteristics of Brazilian older people with a new episode of LBP presenting to primary care.Methods
We sourced baseline information on socio-demographic, pain-related and clinical characteristics from 602 older adults from the Brazilian Back Complaints in the Elders (Brazilian BACE) study. We analyzed differences in pain, disability, functional capacity and psychosocial factors between sub-groups based on age (i.e. participants aged 55–74 or ≥75 years), education (i.e. those with four years or less of schooling or those with more than four years of schooling) and income (i.e. participants who reported earning two or less minimal wages or three and more).Results
Participants presented severe LBP (7.18/10, SD: 2.59). Younger participants were slightly more disabled (mean difference 1.29 points, 95% confidence interval [CI]: 0.03/5.56), reporting poorer physical health, and less fall-related self-efficacy (mean difference of 2.41, 95% CI 0.35/4.46). Those less educated, and those with income equal or less than two minimum wages had more disability, pain catastrophizing and worse functional capacity.Conclusions
This was the first study showing that Brazilian older adults with LBP present high levels of functional disability and psychological distress, especially those with low socioeconomic status. 相似文献110.
Ana Patrícia LOPES Anabela VILARES Francisco NETO Alcina RODRIGUES Tania MARTINS Idalina FERREIRA Maria Jo?o GARGATé Manuela RODRIGUES Luís CARDOSO 《Iranian Journal of Parasitology》2015,10(3):465-472
Background: Epidemiological investigations on Toxoplasma gondii infection have found a significant association between human toxoplasmosis and consumption of raw or undercooked meat. The present study aimed to characterize genotypes of T. gondii in 20 cattle, 40 sheep, 15 goats and 16 pigs from the North of Portugal.Methods: Nested PCR amplified the surface antigen 2 (SAG2) gene. Sequencing analysis was performed in order to assess the prevalence of SAG2 type strains (I, II and III).
Results: Three and 4 strains of SAG2 type II were identified in heart samples of cattle and sheep, respectively. Three SAG2 type II strains were detected in brain, diaphragm and heart of 3 pigs. Three strains detected in heart samples of 3 goats belonged to SAG2 types I or II; with the same result being observed in heart samples from 2 sheep and in 2 brain and 1 heart samples from 3 pigs.
Conclusion: SAG2 type II has been shown for the first time to infect cattle in North of Portugal. In addition, SAG2 type II has also been confirmed as the predominant strain in sheep and pigs in the same region. This is the first molecular report of T. gondii in goats from Portugal.Key Words: Genotypes, Portugal, Ruminants, Swine, Toxoplasma gondii 相似文献