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31.
We have previously shown that exposure of mice to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) induces activation-like changes in splenic dendritic cells (DC) in the absence of antigen challenge. Since activation of DC reduces their ability to phagocytize antigen, we examined the effects of TCDD on the ability of DC to process and present antigen to antigen-specific T cells and to internalize latex beads. Additionally, the expression of costimulatory and adhesion molecules was examined on DC from TCDD-treated mice injected with allogeneic tumor cells. The ability of DC from C57Bl/6 mice to induce proliferation of keyhole limpet hemocyanin (KLH)-specific 10.5.17 T cells and production of IL-4 was not significantly altered by TCDD exposure, either when KLH was added in vitro or when the mice were injected with KLH prior to DC isolation. In contrast, ovalbumin (OVA) presentation by DC from TCDD-treated Balb/c mice induced enhanced proliferation of OVA-specific D011.10 T cells, although the production of IL-2 and IFN-gamma was not affected. Enhanced in vivo proliferation of adoptively transferred, CFSE-labeled DO11.10 T cells was also observed in TCDD-treated Balb/c mice that were challenged with OVA. TCDD treatment modulated the expression of major histocompatibility complex (MHC) class II, CD24, ICAM-1, CD40, and LFA-1 on splenic DC from C57Bl/6 mice injected with allogeneic tumor cells; however, the effects of TCDD were identical to changes seen previously in nonimmune mice, suggesting that these effects were not antigen-dependent. Finally, TCDD treatment did not affect the ability of splenic DC to internalize latex beads administered in vivo. Taken together, these results suggest that the activation-like changes induced in DC by TCDD do not suppress the ability of DC to process and present antigen, but may enhance their ability to provide activation signals to T cells. This, in turn, may alter the survival of the T cells, the DC, or both, and might lead to dysregulation of the immune response. 相似文献
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OBJECTIVES: Although the EQ-5D has been used with increasing frequency to measure health-related quality of life, to date, the measure's validity has not been examined in Chinese American immigrants. We evaluated the construct validity of the EQ-5D by testing its performance with respect to sociodemographic and clinical characteristics of the population and comparing responses on the EQ dimensions with the SF-36 subscales. METHODS: The study surveyed low-income Chinese patients attending a community health center in New York City's Chinatown. Participants received self-administered versions of the EQ-5D and SF-36 and additional questions regarding demographic and clinical information. RESULTS: 856 patients were approached and data were collected from 523 patients (61%). Analysis of the EQ-5D responses by sociodemographic and clinical variables found significant differences among categories of age, gender, marital status, number of medical problems, self-rated health, and specific medical problems. Correlations between similar dimensions and subscale scores were stronger between the two measures than dissimilar ones. Patients without impairments on a given EQ dimension tended to have higher SF-36 subscale scores than patients reporting 'any' impairment (i.e. some/moderate or severe). CONCLUSIONS: The results provide initial support for the construct validity of the EQ-5D in our sample. Further studies should compare the performance of the EQ-5D with other preference-based measures in Chinese persons and examine the valuations that both low-income and Chinese persons place on core aspects of health. 相似文献
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Tovi Lehmann Douglas H Graham Erica R Dahl Lilian M G Bahia-Oliveira S M Gennari J P Dubey 《Infection, genetics and evolution》2004,4(2):107-114
Previous studies of Toxoplasma gondii, based on samples dominated by clinical isolates, have concluded that its population structure is clonal, despite the sexual reproduction that occurs in cats. To determine whether this applies to non-clinical isolates, we compared patterns of linkage disequilibrium (LD) among seven loci in samples of T. gondii from Brazil and the US. LD was detected in both locations, but it was substantially lower in Brazil. The lower LD in Brazil can be explained by a higher rate of sexual reproduction between different genotypes (outcrossing) because of a higher rate of transmission. The extent of LD between pairs of physically unlinked loci varied significantly in each location. Moreover, the magnitude of LD between corresponding locus pairs in Brazil and the US was correlated, despite minimal gene exchange between the continents (mean FST = 0.19). The heterogeneity among locus pairs and the correlation in LD between physically unlinked locus pairs from different continents suggests that locus-specific factors, such as epistatic selection are involved in maintaining LD in T. gondii. Possibly, the unique life cycle of T. gondii with its unpredictable transmission among diverse host species and distinct ecological habitats requires specific combinations of alleles from multiple loci. The usefulness of typing isolates based on physically unlinked loci is questioned not only by the geographic variation in the reproductive population structure, but mainly by the low overall predictability of the genotype of one locus based on the genotype in another (unlinked) locus. This predictability ranged between 23 and 45%, but was close to nil for a considerable fraction of locus pairs. 相似文献
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Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. 总被引:13,自引:0,他引:13
Stephen Couban Michael Goodyear Margot Burnell Sean Dolan Parveen Wasi David Barnes Darlene Macleod Erica Burton Pantelis Andreou David R Anderson 《Journal of clinical oncology》2005,23(18):4063-4069
PURPOSE: In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer. PATIENTS AND METHODS: Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo. RESULTS: There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test). CONCLUSION: Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively. 相似文献
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Naveenchandra Suryadevara Andrea R. Shiakolas Laura A. VanBlargan Elad Binshtein Rita E. Chen James Brett Case Kevin J. Kramer Erica C. Armstrong Luke Myers Andrew Trivette Christopher Gainza Rachel S. Nargi Christopher N. Selverian Edgar Davidson Benjamin J. Doranz Summer M. Diaz Laura S. Handal Robert H. Carnahan Michael S. Diamond Ivelin S. Georgiev James E. Crowe Jr. 《The Journal of clinical investigation》2022,132(11)
The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2–neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2–transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability. 相似文献
38.
Michael Puckette Victoria Primavera Erica Martel Jose Barrera William Hurtle Benjamin Clark Barbara Kamicker Mariceny Zurita David Brake John Neilan 《Viruses》2022,14(5)
RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses. 相似文献
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Maggie D. Clarke Alexis N. Bosseler Julia C. Mizrahi Erica R. Peterson Eric Larson Andrew N. Meltzoff Patricia K. Kuhl Samu Taulu 《Human brain mapping》2022,43(12):3609
The excellent temporal resolution and advanced spatial resolution of magnetoencephalography (MEG) makes it an excellent tool to study the neural dynamics underlying cognitive processes in the developing brain. Nonetheless, a number of challenges exist when using MEG to image infant populations. There is a persistent belief that collecting MEG data with infants presents a number of limitations and challenges that are difficult to overcome. Due to this notion, many researchers either avoid conducting infant MEG research or believe that, in order to collect high‐quality data, they must impose limiting restrictions on the infant or the experimental paradigm. In this article, we discuss the various challenges unique to imaging awake infants and young children with MEG, and share general best‐practice guidelines and recommendations for data collection, acquisition, preprocessing, and analysis. The current article is focused on methodology that allows investigators to test the sensory, perceptual, and cognitive capacities of awake and moving infants. We believe that such methodology opens the pathway for using MEG to provide mechanistic explanations for the complex behavior observed in awake, sentient, and dynamically interacting infants, thus addressing core topics in developmental cognitive neuroscience. 相似文献