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951.
Di Simplicio P Frosali S Priora R Summa D Cherubini Di Simplicio F Di Giuseppe D Di Stefano A 《Antioxidants & redox signaling》2005,7(7-8):951-963
Protein thiolation is elicited by oxidation by different mechanisms and is involved in a variety of biological processes. Thiols, protein SH (PSH) and non-protein SH groups (NPSH, namely GSH), are in competition in all biological environments in the regulation of oxidant homeostasis because oxidants thiolate proteins, whereas GSH dethiolates them (e.g., GSSG + PSH --> GSSP + GSH). Although poorly investigated, the elimination of disulfides from thiolated proteins to regenerate critical PSH is important. These aspects are poorly known in cells, where glutaredoxin and peroxiredoxin operate as enzymes or potential chaperones to accelerate dethiolation. On the contrary, studies with plasma or albumin have highlighted the importance of protein conformation in dethiolation processes and have clarified the reason why homocysteine (thiol with potential toxicity) is preferentially bound to albumin as protein-thiol mixed disulfide with respect to other NPSH. Here we provide an overview of protein thiolation/dethiolation processes, with an emphasis on recent developments and future perspectives in this field. 相似文献
952.
Chiarini A Dal Pra I Menapace L Pacchiana R Whitfield JF Armato U 《International journal of molecular medicine》2005,16(5):801-807
The accumulation of amyloid beta (Abeta)-peptides and their collection in fibrillar plaques in the human brain are believed to be responsible for Alzheimer's disease. The major neuron killers in the Alzheimer brain include proinflammatory cytokines and NO made by NOS-2 (inducible nitric oxide synthase-2). We have determined the effect of a soluble Abeta peptide, Abeta(1-40), on the expression of NOS-2 in astrocytes using a novel model system consisting of pure cultures of cells from adult human brains that, after the first three passages in vitro, become stably locked into the normal astrocytic phenotype like their counterparts in the adult human brain. Abeta(1-40) alone stimulated quiescent astrocytes to start expressing functional NOS-2 and dumping NO into the culture medium during the next 4 days. But adding three of the proinflammatory cytokines commonly produced in the Alzheimer brain--IFN-gamma, IL-1beta, and TNF-alpha--along with Abeta(1-40) more than trebled NOS-2 expression and doubled NO production. In view of the possibility of myelin breakdown in the Alzheimer brain, we also tested the capability of myelin basic protein (MBP) to stimulate NO production using human astrocytes. We found that MBP mimicked the ability of Abeta(1-40) to induce cells to release NO and adding the cytokine triad along with MBP more than doubled NO production and release. Thus, it appears that Abeta peptides and MBP can join forces with proinflammatory cytokines to enhance the NO-mediated killing of neurons in the Alzheimer brain. 相似文献
953.
The effect of ageing and immobilization on structure and function of human skeletal muscle fibres 总被引:20,自引:2,他引:20
954.
Origone P Defferrari R Mazzocco K Lo Cunsolo C De Bernardi B Tonini GP 《American journal of medical genetics. Part A》2003,(4):309-313
Neurofibromatosis type 1 (NF1) patients are susceptible to tumor development. In the present study we describe a child with NF1 and disseminated neuroblastoma whose death resulted from disease progression. The mother had café-au-lait spots suggesting a familial NF1. Neuroblastoma cells showed MYCN amplification and chromosome 1p36 deletion, common features associated with tumor progression in this malignancy. The NF1 gene displayed a germline T --> C transition of intron 14 in both the proband and mother DNA. This mutation, not yet previously described, occurs in a splicing donor site and produces a new mRNA variant observed together with normal NF1 mRNA. Furthermore, the SSCP analysis of the NF1 gene in tumor cells showed a somatic deletion encompassing the intron 26 and 27b of the paternal NF1 allele. Hence, neuroblastoma cells displayed both somatic and germline mutation of the NF1 gene. Our data suggest that, although rare, neuroblastoma in patients with NF1 may display homozygous gene inactivation. 相似文献
955.
Barbara Alicja Jereczek-Fossa Federica Cattani Alberto D'Onofrio Raffaella Cambria Anna Kowalczyk Anna Corallo Andrea Vavassori Dario Zerini Giovanni Battista Ivaldi Ottavio DeCobelli Roberto Orecchia 《Radiotherapy and oncology》2006,81(3):294-302
PURPOSE: To compare dose distribution for two techniques of 3-dimensional conformal radiotherapy (RT): 6-field technique (6F) and 2-dynamic arc therapy (2DA). METHODS AND MATERIALS: Thirty nonmetastatic prostate cancer patients were included. In each patient, two treatment plans were prepared: with six coplanar fields (45 degrees , 90 degrees , 135 degrees , 225 degrees , 270 degrees , 315 degrees ) and with two dynamic lateral 100 degrees -wide arcs (40-140 degrees , 220-320 degrees ). Dose-volume histograms (DVHs) were computed and mean area under curve (AUC) values were calculated for the DVHs of Planning Target Volume (PTV), rectum, urinary bladder and femoral heads. Doses given to 30% of rectum (DR(30)), to 60% of rectum (DR(60)), to 50% of bladder (DB(50)), to 50% of femoral head (DF(50)) and to 95% of PTV (DPTV(95)) were reported as a percentage of the total dose. RESULTS: Mean DR(30) and DR(60) for 6F and 2DA were 75.8%, 51.5% and 72.2%, 37.2%, respectively. Mean DB(50) for 6F and 2DA were 68% and 64.2%, respectively. Mean right DF(50) for 6F and 2DA were 35.4% and 45.5%, respectively. Mean DPTV(95) for 6F and 2DA were 99% and 99.2%, respectively. Mean AUCs of DVHs of rectum and urinary bladder were significantly higher for 6F (this was more evident for small PTV and in the intermediate dose range). Mean AUC of DVHs of PTV and femoral heads were significantly higher for 2DA. CONCLUSIONS: Both 6F and 2DA offer good dose distribution for PTV. 2DA allows for significantly better sparing of rectum and urinary bladder with slightly worse femoral head dose distribution. Further study is warranted in order to establish the clinical relevance of these differences. 相似文献
956.
Michelandrea De Cesare Graziella Pratesi Silvia Veneroni Raffaella Bergottini Franco Zunino 《Clinical cancer research》2004,10(21):7357-7364
PURPOSE: Gimatecan, a novel oral lipophilic camptothecin characterized by favorable features at molecular/cellular level and by a promising profile of preclinical activity, is currently in clinical phase I/II. The aim of the study was to additionally investigate the therapeutic potential of the drug in human tumor xenografts growing in different organs as models representative of tumor growth in the clinical setting. EXPERIMENTAL DESIGN: The models include two orthotopic central nervous system tumors, two melanomas growing intracranially, and an ovarian carcinoma growing i.p. In addition, gimatecan was tested against experimental lung metastases of two tumor types (lung and ovarian carcinomas). Gimatecan was delivered by oral gavage according to various schedules (daily or intermittent). The time (in days) mice required to show evident signs of disease was used as end point for drug efficacy. RESULTS: Gimatecan was highly effective in delaying disease manifestations in all tumor systems investigated. In the intracranially growing tumors, a significant time increase (versus control mice) was achieved by the drug administered according to all of the schedules. In addition, almost all treated mice were alive and tumor-free at the end of the experiment in the metastatic models and in the ascitic ovarian tumor. The daily prolonged treatment schedule was the best one. CONCLUSIONS: In all tumor systems investigated, including orthotopic tumor growth models and lung metastases, the oral administration of gimatecan showed a therapeutic benefit in terms of survival increase. The good oral availability allowed a prolonged daily treatment regimen, which seems the most promising to exploit the therapeutic potential of the drug. 相似文献
957.
Inhibition of hepatocellular carcinomas in vitro and hepatic metastases in vivo in mice by the histone deacetylase inhibitor HA-But. 总被引:2,自引:0,他引:2
Danila Coradini Sonia Zorzet Raffaella Rossin Ignazio Scarlata Cinzia Pellizzaro Claudia Turrin Michele Bello Silvia Cantoni Annalisa Speranza Gianni Sava Ulderico Mazzi Alberto Perbellini 《Clinical cancer research》2004,10(14):4822-4830
PURPOSE: The purpose is to evaluate the CD44-mediated cellular targeting of HA-But, a hyaluronic acid esterified with butyric acid (But) residues, to hepatocellular carcinoma cell lines in vitro and to hepatic tumor metastases in vivo. EXPERIMENTAL DESIGN: In vitro, the CD44-dependent cytotoxicity in two human hepatocellular carcinoma cell lines (HepB3 and HepG2) with high and low CD44 expression was investigated; in vivo, the effect on liver metastases originating from intrasplenic implants of Lewis lung carcinoma (LL3) or B16-F10 melanoma in mice was compared with the pharmacokinetics of organ and tissue distribution using different routes of administration. RESULTS: HepB3 and HepG2 cell lines showed different expression of CD44 (78 and 18%, respectively), which resulted in a CD44-dependent HA-But inhibitory effect as demonstrated also by the uptake analysis performed using radiolabeled HA-But ((99m)Tc-HA-But). Pharmacokinetic studies showed different rates of (99m)Tc-HA-But distribution according to the route of administration (i.v., i.p., or s.c.): very fast (a few minutes) after i.v. treatment, with substantial accumulation in the liver and spleen; relatively slow after i.p. or s.c. treatment, with marked persistence of the drug at the site of injection. The effect of s.c. and i.p. treatment with HA-But on liver metastases originating from intrasplenic implants of LL3 carcinoma or B16-F10 melanoma (both CD44-positive: 68 and 87%, respectively), resulted in 87 and 100% metastases-free animals, respectively (regardless of the route of administration), and a significant prolongation of the life expectancy compared with control groups. CONCLUSIONS: HA-But tends to concentrate in the liver and spleen and appears to be a promising new drug for the treatment of intrahepatic tumor lesions. 相似文献
958.
959.
Giuseppe Castaldo Emilia Rippa Donatello Salvatore Raffaella Sibillo Valeria Raia Giorgio de Ritis Francesco Salvatore 《American journal of medical genetics. Part A》1997,69(2):155-158
The clinical and laboratory findings of a cystic fibrosis (CF) patient homozygous for the G542X mutation are described. This is the first case, among the 7 G542X homozygous CF subjects described so far who shows severe liver involvement, associated pancreatic insufficiency, and moderate pulmonary expression of the disease, as demonstrated by laboratory and imaging data. This case adds to the conclusion that genotype/phenotype correlation in cystic fibrosis is more complex than formerly suspected. Am. J. Med. Genet. 69:155–158, 1997. © 1997 Wiley-Liss, Inc. 相似文献
960.
Natalia Visalli Maria G. Cavallo Alberto Signore Marco G. Baroni Raffaella Buzzetti Elvira Fioriti Chiara Mesturino Rossana Fiori Lucio Lucentini Maria C. Matteoli Antonio Crin Stefania Corbi Sabrina Spera Carlo Teodonio Francesco Paci Rita Amoretti Luigi Pisano Concetta Suraci Giuseppe Multari Nicoletta Sulli Marco Cervoni Giancarlo De Mattia Maria R. Cassone Faldetta Brunetto Boscherini Maria L. Manca Bitti Giovanni Marietti Federica Ferrazzoli Carla Bizzarri Dario Pitocco Giovanni Ghirlanda Paolo Pozzilli 《Diabetes/metabolism research and reviews》1999,15(3):181-185