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991.
992.
Effros RM Casaburi R Su J Dunning M Torday J Biller J Shaker R 《American journal of respiratory and critical care medicine》2006,173(4):386-392
RATIONALE: Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated "acidopnea," has been attributed to airway inflammation. OBJECTIVES: To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD). METHODS: Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients. RESULTS: The average EBC pH in COPD was reduced (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74-7.64; p = 0.079). EBCs were well buffered by NH(4)(+)/NH(3) and CO(2)/HCO(3)(-) in all but four patients, who had NH(4)(+) concentrations under 60 micromol/L, and acetate concentrations that approached or exceeded those of NH(4)(+). Saliva contained high concentrations of acetate (approximately 6,000 micromol/L) and NH(4)(+) (approximately 12,000 micromol/L). EBC acetate increased and EBC NH(4)(+) decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (approximately 1:12,000). Transfer of both acetic acid and NH(3) from the saliva to the EBC was in the gas phase rather than droplets. CONCLUSIONS: EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea. 相似文献
993.
Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome 总被引:1,自引:0,他引:1 下载免费PDF全文
Joanna Groom Susan L. Kalled Anne H. Cutler Carl Olson Stephen A. Woodcock Pascal Schneider Jurg Tschopp Teresa G. Cachero Marcel Batten Julie Wheway Davide Mauri Dana Cavill Tom P. Gordon Charles R. Mackay Fabienne Mackay 《The Journal of clinical investigation》2002,109(1):59-68
BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sj?gren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis. 相似文献
994.
Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance 总被引:11,自引:0,他引:11
Oppenheim DE Roberts SJ Clarke SL Filler R Lewis JM Tigelaar RE Girardi M Hayday AC 《Nature immunology》2005,6(9):928-937
Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'immunoevasion'. Investigating this paradox, we report here that constitutive Rae-1epsilon transgene expression in normal epithelium elicited local and systemic NKG2D downregulation, generalized but reversible defects in NK cell-mediated cytotoxicity and mild CD8(+) T cell defects. The extent of NKG2D downregulation correlated well with the incidence and progression of cutaneous carcinogenesis, emphasizing the utility of NKG2D as a marker of tumor resistance. Thus, NKG2D engagement is a natural mediator of immunosurveillance, which can be compromised by locally sustained ligand expression but potentially restored by innate immune activation. 相似文献
995.
Fluorescent amplified fragment length polymorphism genotyping of Campylobacter jejuni and Campylobacter coli strains and its relationship with host specificity, serotyping, and phage typing 总被引:4,自引:0,他引:4 下载免费PDF全文
Fluorescent amplified fragment length polymorphism (FAFLP) analysis was applied to 276 Campylobacter jejuni strains and 87 Campylobacter coli strains isolated from humans, pigs, cattle, poultry, and retail meats to investigate whether certain FAFLP genotypes of C. jejuni and C. coli are associated with a particular host and to determine the degree of association between FAFLP-defined genotypes and heat-stable serotypes and/or phage types. Within C. coli, the poultry strains clustered separately from those of porcine origin. In contrast, no evidence of host specificity was detected among C. jejuni strains. While C. coli strains show host specificity by FAFLP genotyping, C. jejuni strains that are genotypically similar appear to colonize a range of hosts, rather than being host adapted. Some serotypes and/or phage types (C. jejuni serotype HS18, phage type PT6, and serophage type HS19/PT2 and C. coli HS66, PT2, and HS56/PT2) were the most homogeneous by FAFLP genotyping, while others were more heterogeneous (C. jejuni HS5 and PT39, and C. coli HS24 and PT44) and therefore poor indicators of genetic relatedness between strains. The lack of host specificity in C. jejuni suggests that tracing the source of infection during epidemiological investigations will continue to be difficult. The lack of congruence between some serotypes and/or phage types and FAFLP genotype underlines the need for phenotypic testing to be supplemented by genotyping. This study also demonstrates how, in general, FAFLP generates "anonymous" genetic markers for strain characterization and epidemiological investigation of Campylobacter in the food chain. 相似文献
996.
Simultaneous quantification of isoniazid,rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry 下载免费PDF全文
Julie B. Prahl Marika Lundqvist Justyna M. C. Bahl Isik S. Johansen Åse B. Andersen Niels Frimodt‐Møller Arieh S. Cohen 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2016,124(11):1004-1015
A remediable cause of poor treatment response in drug‐susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first‐line anti‐TB drugs. The aim of this work was to develop an accurate and precise LC‐MS/MS method for simultaneous quantification of all four first‐line anti‐TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed‐Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5–10 mg/L, for rifampicin 0.75–30 mg/L, for ethambutol 0.25–10 mg/L and for pyrazinamide 4–80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC‐MS/MS method can readily be used for simultaneous quantification of first‐line anti‐TB drugs in plasma and is well suited for TDM. 相似文献
997.
Ramos B Núñez M Martín-Carbonero L Sheldon J Rios P Labarga P Romero M Barreiro P García-Samaniego J Soriano V 《Journal of acquired immune deficiency syndromes (1999)》2007,44(5):557-561
BACKGROUND: Differences in subtypes, hepatitis B early antigen (HBeAg)-negative variants, and drug resistance mutations all seem to influence the clinical and therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection. Information available on the prevalence and distribution of distinct HBV variants in HIV-positive patients is scarce. METHODS: All HIV-infected patients with persistent serum hepatitis B surface antigen and detectable HBV viremia were identified in a reference HIV clinic located in Madrid, Spain. HBV load, subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine (LAM) resistance mutations were analyzed. RESULTS: A total of 81 HBV/HIV-coinfected patients (4.1%) were identified in a population of 1968 HIV-positive patients. Plasma specimens with detectable HBV viremia could be obtained from 62 subjects, and this was the study population that underwent further virologic characterization. HBV genotype distribution was as follows: A (n = 27), D (n = 27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes (A/E and A/F). HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas HBV-D was most frequent (74%) among intravenous drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40 months; patients with HBV-A tended to show LAM resistance mutations more often (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant, was found in 1 individual. In the multivariate analysis, patients with LAM resistance mutations were significantly more frequently HBeAg-positive and older than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%) of these 62 HBV viremic patients, with no association with specific HBV variants. CONCLUSION: Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and LAM-resistant mutants, in HBV/HIV-coinfected patients. 相似文献
998.
Joshua J. Avila Julie A. Gutierres Megan E. Sheehy Ingrid E. Lofgren Matthew J. Delmonico 《European journal of applied physiology》2010,109(3):517-525
The impact of resistance training has not been thoroughly examined in overweight older adults undergoing weight loss. Subjects
(n = 27) were overweight and obese (BMI 31.7 ± 3.6 kg/m2) older (age 67 ± 4 years) adults and were randomized into either a 10-week Dietary Approaches to Stop Hypertension for weight
loss diet (DASH, n = 12) or DASH plus moderate intensity resistance training (DASH-RT, n = 15). Outcomes included weight loss, total body and mid-thigh composition, muscle and physical function. There were no significant
weight loss differences between the DASH-RT and DASH groups (−3.6 ± 0.8 vs. −2.0 ± 0.9%, p = 0.137). The DASH-RT group had a greater reduction in body fat than the DASH group (−4.1 ± 0.9 vs. −0.2 ± 1.0 kg, p = 0.005). The DASH-RT group had greater changes in lean mass (+0.8 ± 0.4 vs. −1.4 ± 0.4 kg, p = 0.002) and strength (+60 ± 18 vs. −5 ± 9 N, p = 0.008) than the DASH group. There were favorable changes in mid-thigh composition variables in the DASH-RT group that were
different than the lack of changes observed in the DASH group, except for intermuscular adipose tissue. Both groups experienced
decreases in 400-m walk times showed (DASH −36 ± 11 s, DASH-RT −40 ± 7 s) with no differences between groups. Moderate intensity
resistance training during weight loss appears to improve fat mass and thigh composition, but weight loss only does not. However,
global measures of physical functioning may improve with a weight loss-only program. 相似文献
999.
1000.
Roy CJ Warfield KL Welcher BC Gonzales RF Larsen T Hanson J David CS Krakauer T Bavari S 《Infection and immunity》2005,73(4):2452-2460
Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently emulate human responses to these toxins. Here, we report that human leukocyte antigen-DQ8 (HLA-DQ8) transgenic (Tg) mice, but not littermate controls, succumbed to lethal shock induced by SEB aerosols without potentiation. Substantial amounts of perivascular edema and inflammatory infiltrates were noted in the lungs of Tg mice, similar to the pathology observed in nonhuman primates exposed by aerosol to SEB. Furthermore, the observed pathologies and lethal shock correlated with an upsurge in proinflammatory cytokine mRNA gene expression in the lungs and spleens, as well as with marked increases in the levels of proinflammatory circulating cytokines in the Tg mice. Unlike the case for littermate controls, telemetric evaluation showed significant hypothermia in Tg mice exposed to lethal doses of SEB. Taken together, these results show that this murine model will allow for the examination of therapeutics and vaccines developed specifically against SEB aerosol exposure and possibly other bacterial superantigens in the context of human MHC class II receptors. 相似文献