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排序方式: 共有854条查询结果,搜索用时 250 毫秒
31.
32.
Hume GE Fowler EV Doecke J Simms LA Huang N Palmieri O Griffiths LR Florin TH Annese V Radford-Smith GL 《Inflammatory bowel diseases》2008,14(5):585-590
BACKGROUND: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll-like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta-analysis. METHODS: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case-control analysis prior to and after stratification by NOD2 genotype. Genotype-phenotype relationships were also sought. Meta-analysis was conducted via RevMan. RESULTS: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta-analysis of 11 CD cohorts identified a 1.5-fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). CONCLUSIONS: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes. 相似文献
33.
Richard A Brogan Christopher J Malkin Philip D Batin Alexander D Simms James M McLenachan Christopher P Gale 《World journal of cardiology》2014,6(8):865-873
Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed. 相似文献
34.
Joel L. Pederson Melissa S. Chapot Steven R. Simms Reza Sohbati Tammy M. Rittenour Andrew S. Murray Gary Cox 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(36):12986-12991
Rock art compels interest from both researchers and a broader public, inspiring many
hypotheses about its cultural origin and meaning, but it is notoriously difficult to
date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are
among the most debated examples; hypotheses about its age span the entire Holocene
epoch and previous attempts at direct radiocarbon dating have failed. We provide
multiple age constraints through the use of cross-cutting relations and new and
broadly applicable approaches in optically stimulated luminescence dating at the
Great Gallery panel, the type section of BCS art in Canyonlands National Park,
southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation
of the alcove containing the panel, and limits are also set by our related research
dating both a rockfall that removed some figures and the rock’s exposure
duration before that time. Results provide a maximum possible age, a minimum age, and
an exposure time window for the creation of the Great Gallery panel, respectively.
The only prior hypothesis not disproven is a late Archaic origin for BCS rock art,
although our age result of A.D. ∼1–1100 coincides better with the
transition to and rise of the subsequent Fremont culture. This chronology is for the
type locality only, and variability in the age of other sites is likely.
Nevertheless, results suggest that BCS rock art represents an artistic tradition that
spanned cultures and the transition from foraging to farming in the region.Archaeology is focused upon material records, contextualized in
time. Rock art is a record with the potential to provide unique insight into the dynamics
and evolution of culture, but it generally lacks stratigraphic or chronologic context.
Interpretation of the origin and meaning of rock art is indirect at best, or simply
speculative. In the case of some pictographs, pigments may include or have enough accessory
carbon for accelerator mass spectrometry (AMS) radiocarbon dating (1–4). In other special situations, such as
caves, minimum age constraints have been obtained by various techniques of dating material
that overlies or entombs rock art (5–7). However,
most rock art remains undatable and researchers rely upon stylistic comparison and indirect
associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the
most compelling and debated rock art in the United States—the Barrier Canyon style
(BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have
failed and its age remains unknown, with widely ranging hypotheses that have remained
untested until now.The continued development of dating techniques offers new possibilities for hypothesis
testing. The optically stimulated luminescence (OSL) signals from mineral grains make it
possible to date the deposition of most sediment that is exposed to a few seconds of full
sunlight before burial, and its use in the earth and cultural sciences has greatly
increased (10, 11). Among the latest applications of OSL are techniques dating the outer
surfaces of rock clasts that have become shielded from light, including those with
archaeological context (12–15). Recent work has furthermore used the “bleaching” profile of
decreasing luminescence signal toward the surface of rock to estimate exposure time to
sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new
insight into past cultures and landscapes.Here, we synthesize results from three approaches to dating the type section of BCS art,
the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the
full alluvial stratigraphy and a rockfall event that both have incontrovertible
cross-cutting relations with the rock art, and then by determining the exposure duration of
a painted rock surface, we greatly narrow the window of time when the rock art was created.
These approaches do not require direct sampling of rock art and have strong potential for
application to other archaeological and surface processes research. Although our results
are only for the type section of BCS art, and chronological variability should be expected
for the style across the region, they suggest that BCS art coincides with the transition to
agriculture in the northern Colorado Plateau and may not have been limited to a specific
archaeological culture. 相似文献
35.
Vivien M. Hsu Lorinda Chung Laura K. Hummers Fredrick Wigley Robert Simms Marcy Bolster Rick Silver Aryeh Fischer Monique E. Hinchcliff John Varga Avram Z. Goldberg Chris T. Derk Elena Schiopu Dinesh Khanna Lee S. Shapiro Robyn T. Domsic Thomas Medsger Maureen D. Mayes Daniel Furst Mary E. Csuka Jerry A. Molitor Firas Alkassab Virginia D. Steen 《Seminars in arthritis and rheumatism》2014
36.
Autumn R. Meek Gordon A. Simms Donald F. Weaver 《Journal of psychiatry & neuroscience : JPN》2013,38(4):269-275
Background
Alzheimer disease is a neurodegenerative disorder that progresses with marked interindividual clinical variability. We postulate the existence of endogenous molecules within the human brain exerting an antiaggregant activity that will prevent/slow Alzheimer disease progression.Methods
We performed in silico studies to determine if the small endogenous molecules L-phosphoserine (L-PS) and 3-hydroxyanthranilic acid (3-HAA) could bind to the target region of β-amyloid responsible for protein misfolding. In vitro assays measured the antiaggregation effect of these molecules at varying concentrations.Results
In silico studies demonstrated that L-PS and 3-HAA, both endogenous brain molecules, were capable of binding to the histidine13–histidine–glutamine–lysine16 (HHQK) region of β-amyloid involved in misfolding: these interactions were energetically favoured. The in vitro assays showed that both L-PS and 3-HAA were capable of inhibiting β-amyloid aggregation in a dose-dependent manner, with 3-HAA being more potent than L-PS.Limitations
Studies were performed in silico and in vitro but not in vivo.Conclusion
We successfully identified 2 endogenous brain molecules, L-PS and 3-HAA, that were capable of binding to the region of β-amyloid that leads to protein misfolding and neurotoxicity. Both L-PS and 3-HAA were able to inhibit β-amyloid aggregation in varying concentrations; levels of these compounds in the brain may impact their effectiveness in slowing/preventing β-amyloid aggregation. 相似文献37.
Initial assessment on the impact of crystalloids versus colloids during damage control resuscitation
Chrissy Guidry Elizabeth Gleeson Eric R. Simms Lance Stuke Peter Meade Norman E. McSwain Jr Juan C. Duchesne 《The Journal of surgical research》2013
Background
High ratios of fresh frozen plasma:packed red blood cells in damage control resuscitation (DCR) are associated with increased survival. The impact of volume and type of resuscitative fluid used during high ratio transfusion has not been analyzed. We hypothesize a difference in outcomes based on the type and quantity of resuscitative fluid used in patients that received high ratio DCR.Methods
A matched case control study of patients who received transfusions of ≥ four units of PRBC during damage control surgery over 4 1/2 y, was conducted at a Level I Trauma Center. All patients received a high ratio DCR, >1:2 of fresh frozen plasma:packed red blood cells. Demographics and outcomes of the type and quantity of resuscitative fluids used in combination with high ratio DCR were compared and analyzed. A Kaplan-Meier survival analysis was computed among four groups: colloid (median quantity = 1.0 L), <3 L crystalloid, 3–6 L crystalloid, and >6 L crystalloid.Results
There were 56 patients included in the analysis (28 in the crystalloid group and 28 in the colloid group). Demographics were statistically similar. Intraoperative median units of PRBC: crystalloid versus colloid groups was 13 (IQR 8-21) versus 16 (IQR 12–19), P = 0.135; median units of FFP: 12 (IQR 7–18) versus 12 (IQR 10–18), P = 0.440. OR for 10-d mortality in the crystalloid group was 8.41 [95% CI 1.65–42.76 (P = 0.01)]. Kaplan-Meier survival analysis demonstrated lowest mortality in the colloid group and higher mortality with increasing amounts of crystalloid (P = 0.029).Conclusions
During high ratio DCR, resuscitation with higher volumes of crystalloids was associated with an overall decreased survival, whereas low volumes of colloid use were associated with increased survival. In order to improve outcomes without diluting the survival benefit of hemostatic resuscitation, guidelines should focus on effective low volume resuscitation when high ratio DCR is used. A multi-institutional analysis is needed in order to validate these results. 相似文献38.
DNA microsatellite instability and mismatch repair protein loss in adenomas presenting in hereditary non-polyposis colorectal cancer 总被引:12,自引:0,他引:12 下载免费PDF全文
Iino H Simms L Young J Arnold J Winship IM Webb SI Furlong KL Leggett B Jass JR 《Gut》2000,47(1):37-42
BACKGROUND AND AIM: Hereditary non-polyposis colorectal cancer (HNPCC), as its name implies, is associated with few adenomas, and the early evolution of colorectal neoplasia is poorly understood. In this study our aim was to clarify the genetic profiles of benign polyps in subjects with HNPCC using a combined molecular and immunohistochemical approach. METHODS: Thirty adenomas and 17 hyperplastic polyps were obtained from 24 affected HNPCC subjects. DNA was extracted from paraffin embedded tissue by microdissection and analysed for the presence of microsatellite instability (MSI) and mutations in five genes known to be targets in mismatch repair deficiency (TGFbetaRII, IGF2R, BAX, hMSH3, and hMSH6). Serial sections were stained by immunohistochemistry for hMLH1 and hMSH2. RESULTS: Twenty four (80%) of 30 adenomas showed MSI. Of MSI positive adenomas, 66.7% showed MSI at more than 40% of markers (high level of MSI (MSI-H)). Two of 17 hyperplastic polyps revealed MSI at one marker (low level of MSI (MSI-L)). A significant association was found between MSI-H and high grade dysplasia in adenomas (p=0.004). Eight of nine adenomas with mutations of coding sequences revealed high grade dysplasia and all nine were MSI-H. Four of the nine ranged in size from 2 to 5 mm. The presence of the hMSH6 mutation was significantly correlated with high levels of MSI (80% of markers) (p<0.02). Twenty four adenomas gave evaluable results with immunohistochemistry. One of six (17%) microsatellite stable, six of seven (86%) MSI-L, and 11 of 11 (100%) MSI-H adenomas showed loss of either hMLH1 or hMSH2. CONCLUSIONS: Most adenomas in subjects with a definite diagnosis of HNPCC show MSI (80%). The finding of MSI-L is usually associated with loss of expression of hMLH1 or hMSH2, unlike the situation in MSI-L sporadic colorectal cancer. The transition from MSI-L to MSI-H correlated with the finding of high grade dysplasia and mutation of coding sequences and may be driven by mutation of secondary mutators such as hMSH3 and hMSH6. Advanced genetic changes may be present in adenomas of minute size. 相似文献
39.
ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. V. CHEMICAL COMPOSITION OF ENZYMATICALLY SYNTHESIZED DEOXYRIBONUCLEIC ACID 总被引:5,自引:0,他引:5 下载免费PDF全文
40.