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71.
Murine neutrophils treated with alphaB‐crystallin reduce IL‐12p40 production by dendritic cells 下载免费PDF全文
Neutrophils are essential in the fight against invading pathogens. They utilize antimicrobial effector mechanisms, such as phagocytosis, release of proteases and other antimicrobial products, robust oxidative bursts and neutrophil extracellular traps to combat infections. Neutrophils also modulate immune responses through the production of eicosanoids, cytokines and chemokines, as well as via direct communication with other immune cells. This system of high‐intensity offense against pathogens is exquisitely balanced through regulation to limit damage to host tissue. Unfortunately, the control of neutrophils is not failproof. In cases of sterile injury, autoimmunity and even during an infection, neutrophils can cause tissue destruction and become detrimental to the host. For that reason, there is a need to find means to regulate the aberrant activation of these cells. We found that alphaB‐crystallin (αBC), a heat‐shock protein known to have anti‐inflammatory abilities, affects certain properties of mouse neutrophils that subsequently influence the pro‐inflammatory state of antigen‐presenting cells (APCs). More specifically, αBC mediated small but significant increases in the levels of IL‐10 and matrix metalloproteinase 8, and altered hydrogen peroxide secretion by stimulated neutrophils. Further, the heat‐shock protein influenced the communication between neutrophils and dendritic cells by decreasing the production of pro‐inflammatory cytokines, specifically IL‐12p40, by the APCs. αBC could thus contribute to dampening neutrophil inflammatory responses by impacting the effect of neutrophils on other immune cells. 相似文献
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73.
Park H Bhalla R Saigal R Radisic M Watson N Langer R Vunjak-Novakovic G 《Journal of tissue engineering and regenerative medicine》2008,2(5):279-287
Electrical stimulation affects the deposition of extracellular matrices and cellular differentiation. Type I collagen is one of the most abundant extracellular matrix proteins; however, not much is known about the effects of electrical stimulation on collagen type I deposition in C2C12 cells. Thus, we studied the effects of electrical voltage and stimulation frequency in 3D cultured C2C12 muscle cells in terms of metabolic activity, type I collagen deposition and cell morphology. Electrically excitable C2C12 muscle cells were seeded in collagen scaffolds and stimulated with rectangular signals of voltage (2, 5, 7 V) and frequency (1, 2 Hz), using parallel carbon electrodes spaced 1 cm apart. Metabolic activity was quantified by the glucose:lactate concentration ratio in the medium. Apoptotic activity was assessed by TUNEL staining and changes in collagen deposition were identified by immunohistology. The ultrastructure of the tissue was examined by TEM. Glucose and lactate analysis indicated that all groups had similar metabolic activity. TUNEL stain showed no significant difference in apoptotic damage induced by electrical stimulation compared to the control. Samples stimulated at 2 Hz exhibited reduced collagen deposition compared to the control and 1 Hz stimulated samples. Muscle-protein marker desmin was highly expressed in constructs stimulated with 1 Hz/5 V sample. TEM revealed that the stimulated samples developed highly organized sarcomeres, which coincided with improved contractile properties in the 1 Hz/5 V- and 2 Hz/5 V-stimulated groups. Our data implicate that a specific electrical frequency may modulate type I collagen accumulation and a specific voltage may affect the differentiation of muscle sarcomeres in excitable cells. 相似文献
74.
Liappas IA Nicolaou C Chatzipanagiotou S Tzavellas EO Piperi C Papageorgiou C Boufidou F Bagos P Soldatos CR 《Clinical biochemistry》2007,40(11):781-786
Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals. 相似文献
75.
Bertrand Isidor Frédéric Ebstein Anna Hurst Marie Vincent Ingrid Bader Natasha L. Rudy Benjamin Cogne Johannes Mayr Anja Brehm Caleb Bupp Kathryn Warren Carlos A. Bacino Amanda Gerard Judith D. Ranells Kay A. Metcalfe Yolande van Bever Yong-Hui Jiang Bryce A. Mendelssohn PaweƗ Stankiewicz 《Genetics in medicine》2022,24(1):179-191
PurposeHaploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS.MethodsWe report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status.ResultsThe expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes.ConclusionWe refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature. 相似文献
76.
目的 探讨甲醛对人脐静脉内皮细胞的损伤作用及可能机制。方法 将人脐静脉内皮细胞暴露于不同浓度甲醛(0、5、10、20、40、80μmol/L)下;同时以过氧化氢为阳性对照组,抗氧化药物维生素C为保护组。24h后通过MTT比色法检测细胞生长抑制率,硫代巴比妥酸比色法检测丙二醛含量,观察甲醛是否对内皮细胞具有损伤作用及维生素C对甲醛损伤的内皮细胞是否具有保护作用。结果 甲醛能抑制细胞的生长活性,细胞生长抑制率随甲醛浓度的增加而增加;甲醛诱导细胞外丙二醛的生成,且其含量随甲醛浓度的增加而增加。维生素C能降低甲醛对内皮细胞的生长抑制率,降低细胞外MDA含量。结论 甲醛能诱导内皮细胞产生损伤作用,这种作用与其增加内皮细胞产生过多的脂质过氧化物有关。抗氧化刺维生素C能减轻甲醛对内皮细胞的氧化损伤。 相似文献
77.
Neha Gupta Mariavittoria D'Acierno Enrica Zona Giovambattista Capasso Miriam Zacchia 《American journal of medical genetics. Part C, Seminars in medical genetics》2022,190(1):9-19
Bardet–Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major diagnosis in western countries. It is well established that eight BBS proteins, namely BBS1, 2, 4, 5, 7, 8, 9, and 18, form the BBSome, a multiprotein complex serving as a regulator of ciliary membrane protein composition. Less information is available for BBS6, BBS10, and BBS12, three proteins showing sequence homology with the CCT/TRiC family of group II chaperonins. Even though their chaperonin function is debated, scientific evidence demonstrated that they are required for initial BBSome assembly in vitro. Recent studies suggest that genotype may partially predict clinical outcomes. Indeed, patients carrying truncating mutations in any gene show the most severe phenotype; moreover, mutations in chaperonin-like BBS proteins correlated with severe kidney impairment. This study is a critical review of the literature on genetics, expression level, cellular localization and function of BBS proteins, focusing primarily on the chaperonin-like BBS proteins, and aiming to provide some clues to understand the pathomechanisms of disease in this setting. 相似文献
78.
Omar Abuyaman Niels Torring Rima Obeid Ebba Nexo 《Scandinavian journal of clinical and laboratory investigation》2016,76(8):641-644
Background: Human placenta expresses CD320, a receptor that ensures the uptake of holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the circulation and its concentration increases during pregnancy.Aims: To investigate a possible association of sCD320, holoTC and total transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy.Study design: This study was a retrospective case-control study that we performed on biobank serum samples. Cases (n?=?50) and controls (n?=?198) (matched for gestational age and date of sample collection) were asymptomatic women in early pregnancy [median (range) gestational age?=?10 (8–12) weeks]. Cases developed preeclampsia while the controls remained normotensive throughout pregnancy. We measured the serum concentration of sCD320, holoTC, and total TC by using in-house ELISA methods.Results: First trimester median concentrations of sCD320, holoTC and total TC were not significantly different between cases and controls. The odd ratio for developing preeclampsia based on exposure to low or high levels of sCD320, holoTC or total TC at first trimester was not significant. The reference intervals (2.5–97.5% percentiles (median)) derived from the controls were 50–170 (90) pmol\L for sCD320, 20–140 (70) pmol\L for holoTC and 560–1300 (810) pmol\L for total TC.Conclusions: The risk of preeclampsia is not predicted by first trimester serum concentrations of sCD320, holoTC or total TC. The first trimester reference intervals for the three parameters is reported. 相似文献
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