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排序方式: 共有1454条查询结果,搜索用时 78 毫秒
51.
52.
Volodya Hayrapetyan Stephen Castro Tatyana Sukharnikova Chunxiu Yu Xinyu Cao Yong‐Hui Jiang Henry H. Yin 《The European journal of neuroscience》2014,39(6):1018-1025
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation and impaired speech. Because patients with this disorder often exhibit motor tremor and stereotypical behaviors, which are associated with basal ganglia pathology, we hypothesized that AS is accompanied by abnormal functioning of the striatum, the input nucleus of the basal ganglia. Using mutant mice with maternal deficiency of AS E6‐AP ubiquitin protein ligase Ube3a (Ube3am?/p+), we assessed the effects of Ube3a deficiency on instrumental conditioning, a striatum‐dependent task. We used whole‐cell patch‐clamp recording to measure glutamatergic transmission in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Ube3am?/p+ mice were severely impaired in initial acquisition of lever pressing. Whereas the lever pressing of wild‐type controls was reduced by outcome devaluation and instrumental contingency reversal, the performance of Ube3am?/p+ mice were more habitual, impervious to changes in outcome value and action–outcome contingency. In the DMS, but not the DLS, Ube3am?/p+ mice showed reduced amplitude and frequency of miniature excitatory postsynaptic currents. These results show for the first time a selective deficit in instrumental conditioning in the Ube3a deficient mouse model, and suggest a specific impairment in glutmatergic transmission in the associative corticostriatal circuit in AS. 相似文献
53.
Paolo Gritti Luigi Andrea Lanterna Lidia Rotasperti Matteo Filippini Simone Cazzaniga Carlo Brembilla Tatyana Sarnecki Ferdinando Luca Lorini 《Journal of anesthesia》2014,28(5):687-695
Purpose
Knowledge of the cumulative balance of sodium (CBS) is important for the diagnosis of salt disorders and water homeostasis and has the potential to predict hypovolemic status in acute neurological patients. However, an extensive application of the use of CBS is still lacking in the intensive care setting, where salt and water homeostasis represents a priority.Methods
Records of consecutive series of acute neurological patients admitted to a neurointensive care unit over a 6-month period were retrospectively reviewed. CBS was calculated at the admission to the Emergency Department. Discrimination between cerebral salt-wasting syndrome (CSWS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was performed on the basis of the classical criteria. Additionally, we used the findings of a negative CBS exceeding 2 mEq/kg for the diagnosis of CSWS. Two independent clinicians who were blinded to the CBS results performed diagnosis of the causes of hyponatremia and estimated the daily volemic status of the patients on the basis of clinical parameters. Logistic regression analysis was used to determine the independent prognostic factors of hypovolemia.Results
Thirty-five patients were studied for a total of 418 days. Four patients (11.4 %) fitted the criteria of CSWS and three patients (8.5 %) had SIADH. The unavailability of the CBS led to a wrong diagnosis in three of the eight hyponatremic patients (37.5 %). The risk of developing hypovolemia in patients with negative CBS was 7.1 times higher (CI 3.86–13.06; p < 0.001). Multivariate analysis revealed that negative cumulative fluid balance, negative CBS >2 mEq/kg, and CVP ≤5 cmH2O were independent prognostic factors for hypovolemia.Conclusions
CBS is likely to be a useful parameter in the diagnosis of CSWS and a surrogate parameter for estimating hypovolemia in acute neurological patients. 相似文献54.
Tatyana Danyukova Nataniel F. Ludwig Renata V. Velho Frederike L. Harms Nilay Güne Henning Tidow Ida V. Schwartz Beyhan Tüysüz Sandra Pohl 《Human mutation》2020,41(1):133-139
Mucolipidosis (ML) II and III alpha/beta are inherited lysosomal storage disorders caused by mutations in GNPTAB encoding the α/β‐precursor of GlcNAc‐1‐phosphotransferase. This enzyme catalyzes the initial step in the modification of more than 70 lysosomal enzymes with mannose 6‐phosphate residues to ensure their intracellular targeting to lysosomes. The so‐called stealth domains in the α‐ and β‐subunit of GlcNAc‐1‐phosphotransferase were thought to be involved in substrate recognition and/or catalysis. Here, we performed in silico alignment analysis of stealth domain‐containing phosphotransferases and showed that the amino acid residues Glu389, Asp408, His956, and Arg986 are highly conserved between different phosphotransferases. Interestingly, mutations in these residues were identified in patients with MLII and MLIII alpha/beta. To further support the in silico findings, we also provide experimental data demonstrating that these four amino acid residues are strictly required for GlcNAc‐1‐phosphotransferase activity and thus may be directly involved in the enzymatic catalysis. 相似文献
55.
Juliana F. da Silva Roberto J. Esteves Charlene Siza Elaine P. Soares Tatyana C. Ramos Evelyn C. Campelo Cristiano F. da Costa Leila C. de Alencar Rafaela P. Cavalcante Clerton R. Florêncio Tirza P. Mattos Maria G. Bonecini-Almeida Luciana Silva-Flannery Barbara J. Marston Juliette Morgan Mateusz Plucinski Felipe Naveca CDC Brazil Investigation Team 《Emerging infectious diseases》2022,28(1):262
High case counts after the Gamma (P. 1) variant of severe acute respiratory syndrome coronavirus 2 emerged in Brazil raised concerns that previously infected persons might become reinfected. Investigation of a cluster of coronavirus disease cases in Parintins, in the Brazilian Amazon, suggested household transmission but did not identify high rates of reinfection. 相似文献
56.
Sara Meril Ortal Harush Yishai Reboh Tatyana Matikhina Tilda Barliya Cyrille J. Cohen 《Molecular carcinogenesis》2020,59(7):713-723
Chimeric antigen receptor (CAR) T-cells treatment demonstrate the increasing and powerful potential of immunotherapeutic strategies, as seen mainly for hematological malignancies. Still, efficient CAR-T cell approaches for the treatment of a broader spectrum of tumors are needed. It has been shown that cancer cells can implement strategies to evade immune response that include the expression of inhibitory ligands, such as hypersialylated proteins (sialoglycans) on their surface. These may be recognized by sialic acid-binding immunoglobulin-type lectins (siglecs) which are surface receptors found primarily on immune cells. In this regard, siglec-7 and -9 are found on immune cells, such as natural killer cells, T-cells, and dendritic cells and they can promote immune suppression when binding to sialic acids expressed on target cells. In the present study, we hypothesized that it is possible to use genetically engineered T-cells expressing siglec-based CARs, enabling them to recognize and eliminate tumor cells, in a non-histocompatibility complex molecule restricted way. Thus, we genetically modified human T-cells with different chimeric receptors based on the exodomain of human siglec-7 and -9 molecules and selected optimal receptors. We then assessed their antitumor activity in vitro demonstrating the recognition of cell lines from different histologies. These results were confirmed in a tumor xenograft model exemplifying the potential of the present approach. Overall, this study demonstrates the benefit of targeting cancer-associated glycosylation patterns using CAR based on native immune receptors and expressed in human primary T-cells. 相似文献
57.
58.
Hematopoietic plakophilin‐3 regulates acute tissue‐specific and systemic inflammation in mice
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Tatyana Sklyarova Jolanda van Hengel Elien Van Wonterghem Claude Libert Frans van Roy Roosmarijn E. Vandenbroucke 《European journal of immunology》2015,45(10):2898-2910
Plakophilin‐3 (PKP3) is a member of the armadillo protein family, which is important in cell?cell contacts and signaling during development and tumorigenesis. In conventional facilities, PKP3‐deficient mice (PKP3?/?) develop spontaneous dermatitis, indicating a possible involvement of PKP3 in inflammatory responses. Here, we show that PKP3 deficiency sensitizes mice to irritant contact dermatitis induced by phorbol myristate acetate (PMA). This sensitization occurred in mice with PKP3 deficiency in the hematopoietic system (PKP3?/?hem), but not if the deficiency was specific to skin keratinocytes (PKP3?/?ker). In a model of dextran sulfate sodium induced colitis, ubiquitous PKP3 deletion, but not intestinal epithelial PKP3 deficiency (PKP3?/?IEC), impaired survival from disease. Interestingly, PKP3?/?hem mice also displayed increased sensitivity to dextran sulfate sodium induced colitis. Finally, PKP3?/? mice were more sensitive to the lethality of lipopolysaccharide (LPS) injection than wild‐type (WT) mice, and this phenotype was associated with increased intestinal permeability. PKP3?/?IEC mice did not reproduce the enhanced endotoxin reactivity of PKP3?/? mice, in contrast to PKP3?/?hem mice. Finally, in vitro stimulation of WT neutrophils with LPS or PMA increased Pkp3 expression. In conclusion, our data highlight a novel role for hematopoietic PKP3 in the regulation of both locally and systemically induced immune responses. Nonetheless, further research is needed to unravel the underlying mechanism. 相似文献
59.
M. Cecilia Subauste Tatyana A. Kupriyanova Erin M. Conn Veronica C. Ardi James P. Quigley Elena I. Deryugina 《Clinical & experimental metastasis》2009,26(8):1033-1047
Increased metastatic and angiogenic potentials of aggressive human colon carcinoma cells were verified in independent chick
embryo models by comparing in vivo highly metastatic SW620 colon carcinoma cell line with its isogenic, non-metastatic SW480
cell variant. In the experimental metastasis model, both cell types rapidly arrested in the chorioallantoic membrane (CAM)
vasculature as demonstrated by quantitative PCR and immunohistochemistry. Live cell imaging also indicated that both SW620
and SW480 cells efficiently extravasated from the CAM capillary system. However, only few SW480 cells were present in the
CAM tissue after 24–48 h. In contrast, the numbers of SW620 cells increased exponentially, indicating proliferative and survival
advantages of metastatic colon carcinoma cells in vivo. Multicellular SW620 foci were identified in close proximity to CAM
blood vessels. A positive correlation between increased metastatic ability and VEGF-expression of colon carcinoma SW620 cells
was demonstrated by the substantial inhibitory effects of anti-VEGF treatment on the levels of metastatic colonization and
density of blood vessels adjacent to tumor cell foci. Furthermore, the chick embryo angiogenesis model confirmed high levels
of VEGF-dependent angiogenesis induced by SW620 cells, but not SW480 cells. Thus, chick embryo experimental metastasis and
CAM angiogenesis models appear to coordinately reflect critical features of advanced colon carcinomas, i.e., the acquisition
of enhanced survival and increased angiogenic potentials, both constituting critical determinants of colon cancer progression.
The use of rapid and quantitative chick embryo models might provide alternative approaches to conventional mammalian model
systems for screening anti-cancer agents. 相似文献
60.