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991.
Wichmann O Muehlberger N Jelinek T Alifrangis M Peyerl-Hoffmann G Muhlen M Grobusch MP Gascon J Matteelli A Laferl H Bisoffi Z Ehrhardt S Cuadros J Hatz C Gjorup I McWhinney P Beran J da Cunha S Schulze M Kollaritsch H Kern P Fry G Richter J;European Network on Surveillance of Imported Infectious Diseases 《The Journal of infectious diseases》2004,190(9):1541-1546
BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool. 相似文献
992.
Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat 总被引:1,自引:4,他引:1
Flachs P Horakova O Brauner P Rossmeisl M Pecina P Franssen-van Hal N Ruzickova J Sponarova J Drahota Z Vlcek C Keijer J Houstek J Kopecky J 《Diabetologia》2005,48(11):2365-2375
Aims/hypothesis Intake of n-3 polyunsaturated fatty acids reduces adipose tissue mass, preferentially in the abdomen. The more pronounced effect of marine-derived eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on adiposity, compared with their precursor -linolenic acid, may be mediated by changes in gene expression and metabolism in white fat.Methods The effects of EPA/DHA concentrate (6% EPA, 51% DHA) admixed to form two types of high-fat diet were studied in C57BL/6J mice. Oligonucleotide microarrays, cDNA PCR subtraction and quantitative real-time RT-PCR were used to characterise gene expression. Mitochondrial proteins were quantified using immunoblots. Fatty acid oxidation and synthesis were measured in adipose tissue fragments.Results Expression screens revealed upregulation of genes for mitochondrial proteins, predominantly in epididymal fat when EPA/DHA concentrate was admixed to a semisynthetic high-fat diet rich in -linolenic acid. This was associated with a three-fold stimulation of the expression of genes encoding regulatory factors for mitochondrial biogenesis and oxidative metabolism (peroxisome proliferator-activated receptor gamma coactivator 1 alpha [Ppargc1a, also known as Pgc1] and nuclear respiratory factor-1 [Nrf1] respectively). Expression of genes for carnitine palmitoyltransferase 1A and fatty acid oxidation was increased in epididymal but not subcutaneous fat. In the former depot, lipogenesis was depressed. Similar changes in adipose gene expression were detected after replacement of as little as 15% of lipids in the composite high-fat diet with EPA/DHA concentrate, while the development of obesity was reduced. The expression of Ppargc1a and Nrf1 was also stimulated by n-3 polyunsaturated fatty acids in 3T3-L1 cells.Conclusions/interpretation The anti-adipogenic effect of EPA/DHA may involve a metabolic switch in adipocytes that includes enhancement of -oxidation and upregulation of mitochondrial biogenesis.Electronic Supplementary Material Supplementary material is available in the online version of this article at 相似文献
993.
Vladimir?BalikEmail author Radek?Trojanec Milena?Holzerova Lucie?Tuckova Igor?Sulla Magdalena?Megova Miroslav?Vaverka Lumir?Hrabalek Jiri?Ehrmann 《Neurosurgical review》2015,38(1):1-10
Medulloblastoma (MB), the most common malignant tumor typically affecting children, occurs only exceptionally in adults. Multifocal presentation of this malignancy in adulthood is even much rarer—only four cases with favorable postoperative course have been reported, so far. The study illustrates a very rare rapid postoperative clinical deterioration due to diffuse cerebellar swelling (DCS) in an adult multifocal MB (MMB). To the best of their knowledge, authors for the first time performed genetic analysis of MMB and demonstrated expression patterns of selected markers that put the patient within the sonic hedgehog (SHH) molecular subgroup and at least partially explain her unsatisfactory clinical course. Herein, authors summarized the relevant literature concerning this issue with the aim to determine features that would facilitate diagnosis and therapy of such a scarce clinical entity. 相似文献
994.
Jennifer Y. Lai Jinghui Luo Christopher O’Connor Xiaohong Jing Viji Nair Wenjun Ju Ann Randolph Iddo Z. Ben-Dov Regina N. Matar Daniel Briskin Jiri Zavadil Robert G. Nelson Thomas Tuschl Frank C. Brosius III Matthias Kretzler Markus Bitzer 《Journal of the American Society of Nephrology : JASN》2015,26(4):805-816
TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression of microRNA-21 (miR-21) is regulated by TGF-β1, and miR-21 inhibits apoptosis in cancer cells. TGF-β1–transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β1 and is higher in kidneys of TGF-β1–transgenic mice than wild-type mice. miR-21–deficient TGF-β1–transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-β1–transgenic littermates. Similarly, miR-21 expression was increased in streptozotocin-induced diabetic mice, and loss of miR-21 in these mice was associated with increased albuminuria, podocyte depletion, and mesangial expansion. In cultured podocytes, inhibition of miR-21 was accompanied by increases in the rate of cell death, TGF-β/Smad3-signaling activity, and expression of known proapoptotic miR-21 target genes p53, Pdcd4, Smad7, Tgfbr2, and Timp3. In American-Indian patients with diabetic nephropathy (n=48), albumin-to-creatinine ratio was positively associated with miR-21 expression in glomerular fractions (r=0.6; P<0.001) but not tubulointerstitial fractions (P=0.80). These findings suggest that miR-21 ameliorates TGF-β1 and hyperglycemia-induced glomerular injury through repression of proapoptotic signals, thereby inhibiting podocyte loss. This finding is in contrast to observations in murine models of tubulointerstitial kidney injury but consistent with findings in cancer models. The aggravation of glomerular disease in miR-21–deficient mice and the positive association with albumin-to-creatinine ratio in patients with diabetic nephropathy support miR-21 as a feedback inhibitor of TGF-β signaling and functions. 相似文献
995.
Steffen R Bouchama A Johansson A Dvorak J Isla N Smallwood C Memish ZA 《The Lancet infectious diseases》2012,12(2):142-149
Mass gatherings (MGs) have been associated with high rates of morbidity and mortality from non-communicable diseases, accidents, and terrorist attacks, thus posing complex public health challenges. We assessed the health risks and public health responses to MGs to identify an evidence-based framework for public health interventions. Human stampedes and heat-related illnesses are the leading causes of mortality. Minor traumatic injuries and medical complaints are the main contributors to morbidity and, particularly, the need for on-site medical care. Infrastructure, crowd density and mood, weather, age, and sex determine the risks to health. Many predictive models for deployment of medical resources are proposed, but none have been validated. We identified the risks for mortality and morbidity during MGs, most efficient public health interventions, and need for robust research into health risks for non-communicable diseases during MGs. 相似文献
996.
Christopher R. Chapple Steven A. Kaplan David Mitcheson Jiri Klecka Jana Cummings Ted Drogendijk Caroline Dorrepaal Nancy Martin 《European urology》2013
Background
Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β3-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials.Objective
To assess the 12-mo safety and efficacy of mirabegron.Design, setting, and participants
Patients ≥18 yr of age with OAB symptoms for ≥3 mo.Interventions
After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24 h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50 mg, mirabegron 100 mg, or tolterodine extended release (ER) 4 mg for 12 mo.Outcome measurements and statistical analysis
Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms.Results and limitations
A total of 812, 820, and 812 patients received mirabegron 50 mg, mirabegron 100 mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and −0.5 mm Hg for mirabegron 50 mg, 100 mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation.Conclusions
The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.Trial registration
ClinicalTrials.gov identifier: NCT00688688. 相似文献997.
Jan Hrbacek Michael Urban Eva Hamsikova Ruth Tachezy Jiri Heracek 《Urologic oncology》2013,31(7):951-965
BackgroundThe potential role of genitourinary infection in the etiology of prostate cancer (CaP) has been extensively investigated for 30 years. Two basic approaches have been used: tissue-based methods (polymerase chain reaction, immunohistochemistry, and in situ hybridization) and serologic assays (enzyme-linked immunosorbent assay, immunofluorescence, etc.). The objective of this review was to answer the question of whether infection of the male genitourinary tract may have a role in the etiology of CaP.Materials and methodsWe have carried out a systematic review of the evidence that was published in the MEDLINE/PubMed database until December 2011. The search terms included “prostate cancer,” “infection,” and the explicit names of the various infectious agents. Additional studies were identified using a reference search. A total of 74 papers were included in the review, which cover the following infectious agents: human papillomavirus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human herpesvirus, BK virus, JC virus, chlamydia, mycoplasma, ureaplasma, trichomonas, neisseria, treponema, Propionibacterium acnes, xenotropic murine leukemia virus-related virus and Candida albicans.ResultsDespite the variable study designs and methodological approaches that were used, most of the pathogens that were studied were unlikely to be directly involved in prostate carcinogenesis.ConclusionsThe role of infection in the etiology of CaP has yet to be determined despite 30 years of research efforts. A discovery of an infectious agent that is associated with CaP would be of great medical importance; however, such a link would have to be firmly established before impacting on patient care. 相似文献
998.
Magdalena Megova Jiri Drabek Vladimira Koudelakova Radek Trojanec Ondrej Kalita Marian Hajduch 《Journal of neuroscience research》2014,92(12):1611-1620
Over the past few years, new biomarkers have allowed a deeper insight into gliomagenesis and facilitated the identification of possible targets for glioma therapy. Isocitrate dehydrogenase (IDH) 1 and IDH2 mutations have been shown to be promising biomarkers for monitoring disease prognosis and predicting the response to treatment. This review summarizes recent findings in this field. Web of Science, Science Direct, and PubMed online databases were used to search for publications investigating the role of IDH in glioma. References were identified by searching for the keywords “IDH1 or IDH2 and glioma and diagnostic or predictive or prognostic” in papers published from January, 2008, to April, 2014. Only papers in English were reviewed. Publications available only as an abstract were not included. IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2‐hydroxyglutarate (2HG). Although the contradictory positive effect of IDH mutation on prognosis and negative role of 2HG in tumor transformation remain unresolved, the future direction of personalized treatment strategies targeted to glioma development is likely to focus on IDH1/2 mutations. © 2014 Wiley Periodicals, Inc. 相似文献
999.
1000.
Ondrej Bezdicek David J. Libon Hana Stepankova Erika Panenkova Jiri Lukavsky Kelly Davis Garrett 《The Clinical neuropsychologist》2014,28(7):1162-1181
The aim of the present study was to assess the validity of a 12-word Czech version of the Philadelphia (repeatable) Verbal Learning Test [czP(r)VLT-12]. The construction of the czP(r)VLT-12 was modeled after the California Verbal Learning Test (CVLT) and the nine-word Philadelphia (repeatable) Verbal Learning Test [P(r)VLT]. The czP(r)VLT-12 was constructed from a large corpus of old (60–74) and very old (75–96) Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders and performed within normal limits on other neuropsychological measures. Principal component analysis (PCA) and correlations between czP(r)VLT-12 factor structure and other memory tests were conducted. The czP(r)VLT-12 produced a four-factor solution, accounting for 70.90% of variance, with factors related to: (1) recall, (2) extra-list intrusion errors/recognition foils, (3) interference, and (4) acquisition rate; a solution similar to the CVLT and P(r)VLT. Increasing age resulted in a decline in most czP(r)VLT-12 indices, women outperformed men, and higher education led to higher scores. Memory performance in normal aging did not correlate with instrumental activities of daily living. Low, but significant, correlations were seen with other tests of cognitive performance (divergent validity). Appendices are available that provide normed percentile estimates of individual czP(r)VLT-12 performance stratified by age, education, and gender. In accordance with previous studies, these results demonstrate the usefulness of czP(r)VLT-12 in assessing declarative memory in older adults. 相似文献