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排序方式: 共有831条查询结果,搜索用时 15 毫秒
1.
Carla M van Herpen Maaike Looman Marijke Zonneveld Nicole Scharenborg Peter C de Wilde Louis van de Locht Matthias A W Merkx Gosse J Adema Pieter H de Mulder 《Clinical cancer research》2004,10(8):2626-2635
The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients. Toxicity was high, with unexpected dose-limiting toxicities at the 300 ng/kg dose level. Dose-dependent plasma IFN-gamma and IL-10 increments were detected. These cytokine levels were higher after the first injection than after the subsequent injections. A rapid, transient reduction in lymphocytes, monocytes, and all lymphocyte subsets, especially natural killer cells, was observed, due to a redistribution to the lymph nodes. In the enlarged lymph nodes of the IL-12-treated patients, a higher percentage of natural killer cells and a lower percentage of T-helper cells were found compared with control patients. The same pattern was detected in the infiltrate in the primary tumor. Real-time semiquantitative PCR analysis of peripheral blood mononuclear cells in the peripheral blood showed a transient decrease of T-bet mRNA. Interestingly, the peripheral blood mononuclear cells in the lymph nodes showed a 128-fold (mean) increase of IFN-gamma mRNA. A switch from the Th2 to a Th1 profile in the lymph nodes compared with the peripheral blood occurred in the IL-12-treated patients. In conclusion, in previously untreated head and neck squamous cell carcinoma patients, recombinant human IL-12 intratumorally showed dose-limiting toxicities at the dose level of 300 ng/kg and resulted in measurable immunological responses locoregionally at both dose levels. 相似文献
2.
Thallium-201 single-photon emission computed tomography as an early predictor of outcome in recurrent glioma. 总被引:2,自引:0,他引:2
Maaike J Vos Otto S Hoekstra Frederik Barkhof Johannes Berkhof Jan J Heimans Cees J van Groeningen W Peter Vandertop Ben J Slotman Tjeerd J Postma 《Journal of clinical oncology》2003,21(19):3559-3565
PURPOSE: With limited response rates and potential toxicity of chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. Currently, the assessment of treatment response in glioma patients is based on the combination of radiologic and clinical findings. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is hampered by several pitfalls and is prone to interobserver variability. The aim of this study was to establish the value of thallium-201 single-photon emission computed tomography (201Tl-SPECT) as a predictor of overall survival and response to chemotherapy in recurrent glioma, and to compare the value of 201Tl-SPECT with that of CT and MRI. PATIENTS AND METHODS: We studied patients who underwent CT or MRI and 201Tl-SPECT before chemotherapy (n = 57), and patients who also had undergone CT or MRI and 201Tl-SPECT after two courses of chemotherapy (n = 44). The value of the radiologic variables (CT-MRI tumor size, 201Tl-SPECT tumor size, and maximal tumor intensity) at baseline and at follow-up in predicting overall survival, and the percentage of patients alive and progression-free at 6 months (APF6) were examined using Cox regression and logistic regression analysis. RESULTS: Both at baseline and at follow-up, 201Tl-SPECT maximal tumor intensity was the strongest predictive variable and was inversely related to overall survival and APF6. In particular, progression of maximal tumor intensity after two courses of chemotherapy was a powerful predictor of poor outcome. CONCLUSION: 201Tl-SPECT is superior to conventional CT-MRI in the early prediction of overall survival and response to chemotherapy in patients with recurrent glioma. 相似文献
3.
van Roekel E Goossens L Scholte RH Engels RC Verhagen M 《Journal of child psychology and psychiatry, and allied disciplines》2011,52(10):1044-1051
Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine‐related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support, and loneliness were examined in a longitudinal study spanning five annual waves (N = 307). Results: Using Latent Growth Curve Modeling, DRD2 genotype was not directly related to loneliness. Interactions were found between parental support and DRD2 genotype, showing that adolescents with the A2A2 genotype who perceived little support from their parents had the highest baseline levels of loneliness. Adolescents with an A1 allele were not susceptible to the rewarding effect of parental support. Conclusions: The present study is the first to examine the role of the DRD2 genotype in loneliness. Our results contribute to a further understanding of the environmental and genetic basis of loneliness in adolescence. 相似文献
4.
Linda Broer Christina M. Lill Maaike Schuur Najaf Amin Johannes T. Roehr Lars Bertram John P. A. Ioannidis Cornelia M. van Duijn 《European journal of epidemiology》2013,28(2):131-138
Distinguishing true from false positive findings is a major challenge in human genetic epidemiology. Several strategies have been devised to facilitate this, including the positive predictive value (PPV) and a set of epidemiological criteria, known as the “Venice” criteria. The PPV measures the probability of a true association, given a statistically significant finding, while the Venice criteria grade the credibility based on the amount of evidence, consistency of replication and protection from bias. A vast majority of journals use significance thresholds to identify the true positive findings. We studied the effect of p value thresholds on the PPV and used the PPV and Venice criteria to define usable thresholds of statistical significance. Theoretical and empirical analyses of data published on AlzGene show that at a nominal p value threshold of 0.05 most “positive” findings will turn out to be false if the prior probability of association is below 0.10 even if the statistical power of the study is higher than 0.80. However, in underpowered studies (0.25) with a low prior probability of 1 × 10?3, a p value of 1 × 10?5 yields a high PPV (>96 %). Here we have shown that the p value threshold of 1 × 10?5 gives a very strong evidence of association in almost all studies. However, in the case of a very high prior probability of association (0.50) a p value threshold of 0.05 may be sufficient, while for studies with very low prior probability of association (1 × 10?4; genome-wide association studies for instance) 1 × 10?7 may serve as a useful threshold to declare significance. 相似文献
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6.
Dani?lle Horst Ruben J. Geerdink Anna M. Gram Arie J. Stoppelenburg Maaike E. Ressing 《Viruses》2012,4(10):2379-2399
The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway. 相似文献
7.
Merel Klaassens Deborah Morrogh Elisabeth M Rosser Fatima Jaffer Maaike Vreeburg Levinus A Bok Tim Segboer Martine van Belzen Ros M Quinlivan Ajith Kumar Jane A Hurst Richard H Scott 《European journal of human genetics : EJHG》2015,23(5):610-615
De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype that we propose is referred to as Malan syndrome. Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall–Smith syndrome. We report six additional patients with Malan syndrome and de novo NFIX deletions or sequence variants and review the 20 patients now reported. The phenotype is characterised by moderate postnatal overgrowth and macrocephaly. Median height and head circumference in childhood are 2.0 and 2.3 standard deviations (SD) above the mean, respectively. There is overlap of the facial phenotype with NSD1-positive Sotos syndrome in some cases including a prominent forehead, high anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal feeding difficulties and/or hypotonia have been reported in 30% of patients. Developmental delay/learning disability have been reported in all cases and are typically moderate. Ocular phenotypes are common, including strabismus (65%), nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic ataxia type 2 or familial hemiplegic migraine. One previous case had episodic ataxia and one case we report has had cyclical vomiting responsive to pizotifen. In individuals with this contiguous gene deletion syndrome, awareness of possible later neurological manifestations is important, although their penetrance is not yet clear. 相似文献
8.
Marthe M. de Jonge Dina Ruano Ronald van Eijk Nienke van der Stoep Maartje Nielsen Juul T. Wijnen Natalja T. ter Haar Astrid Baalbergen Monique E.M.M. Bos Marjolein J. Kagie Maaike P.G. Vreeswijk Katja N. Gaarenstroom Judith R. Kroep Vincent T.H.B.M. Smit Tjalling Bosse Tom van Wezel Christi J. van Asperen 《The Journal of molecular diagnostics : JMD》2018,20(5):600-611
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10.
Maaike B. van Werkhoven Jeffrey Damman Mohamed R. Daha Christina Krikke Harry van Goor Willem J. van Son Jan-Luuk Hillebrands Marcory C.R.F. van Dijk Marc A.J. Seelen 《Molecular immunology》2013,53(3):237-245
AimsThe complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown.Materials and resultsRenal C5aR and C5L2 expression and localization were analyzed immunohistochemically. C5aR and C5L2 expression was analyzed in human kidney biopsies obtained from living donors and patients suffering from acute tubular necrosis, acute cellular and vascular rejection or IF/TA.C5aR was expressed in the thick ascending limb of Henle's loop and first part of the distal convoluted tubule (DCT). Under inflammatory conditions, C5aR was de novo expressed in proximal tubuli. C5L2 was expressed in the kidney and localized to DCT1, DCT2 and connecting tubule. Persistent distal tubular expression of both receptors was demonstrated after renal transplantation.ConclusionsThis study shows distinct renal expression patterns for C5aR and C5L2. Our findings suggest a functional role for renal C5L2 rather than being a C5a decoy receptor. Future studies focusing on renal C5a–C5aR interaction should take differential C5aR and C5L2 expression into account, alongside abundant C5aR expression on infiltrating cells. 相似文献