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91.
T R Jeffry Evans Ann Yellowlees Elizabeth Foster Helena Earl David A Cameron Andrew W Hutcheon Robert E Coleman Timothy Perren Christopher J Gallagher Mary Quigley John Crown Alison L Jones Martin Highley Robert C F Leonard Janine L Mansi 《Journal of clinical oncology》2005,23(13):2988-2995
PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC. 相似文献
92.
Mark P Purdue Lynn From Bruce K Armstrong Anne Kricker Richard P Gallagher John R McLaughlin Neil S Klar Loraine D Marrett 《Cancer epidemiology, biomarkers & prevention》2005,14(8):2015-2022
Cutaneous malignant melanomas with histologic evidence of an associated nevus (N+) may have a different risk factor profile from that of melanomas without it (N-). To address this question, a case-only analysis of 932 people with cutaneous malignant melanoma was done to identify etiologic and other factors associated with N+ melanoma. Evidence of an associated nevus was found in 36% of melanomas. N+ melanomas were thinner (Ptrend=0.0009) and more likely to be of the superficial spreading type than other types of melanoma. Subjects with N+ melanomas were younger (Ptrend<0.0001) and reported a higher nevus density on their skin than subjects with N- melanomas [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.6-6.0, for high nevus density versus no nevi]. Indicators of high accumulated sun exposure were less prevalent among subjects with N+ melanomas (OR, 0.3; 95% CI, 0.2-0.4, for melanoma location on the head and neck versus location on trunk; OR, 0.2; 95% CI, 0.1-0.4, for severe solar elastosis adjacent to the melanoma versus no elastosis; OR, 0.2; 95% CI, 0.1-0.4, for lentigo maligna melanoma subtype versus superficial spreading subtype). With the exception of solar elastosis and age, all of the aforementioned variables remained significantly associated with N+ melanomas in multivariate analyses. No associations with self-reported measures of sun exposure, sunburn, or pigmentation phenotype were apparent. Our findings provide some support for the hypothesis of etiologically separate pathways for melanoma, with N+ melanomas appearing less likely to develop in the presence of characteristics suggesting high accumulated sun exposure than N- melanomas. However, it is possible that high UV exposure causes involution of nevi, thus reducing the density of nevi in exposed skin and thereby the probability of N+ melanoma. 相似文献
93.
Jurjees Hasan Steven D Shnyder Andrew R Clamp Alan T McGown Roy Bicknell Marco Presta Michael Bibby John Double Steven Craig David Leeming Kenneth Stevenson John T Gallagher Gordon C Jayson 《Clinical cancer research》2005,11(22):8172-8179
BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin. 相似文献
94.
95.
Jill K. Schinkel Shelia Hoar Zahm Ismail Jatoi Katherine A. McGlynn Christopher Gallagher Catherine Schairer Craig D. Shriver Kangmin Zhu 《Cancer causes & control : CCC》2014,25(8):959-968
Background
Compared to non-inflammatory breast cancer (non-IBC), inflammatory breast cancer (IBC) has less favorable survival and is more likely to be estrogen receptor (ER) and progesterone receptor (PR) negative. ER?/PR? tumors, regardless of histology, have less favorable survival. While black women are more likely to have IBC and ER?/PR? tumors than white women, it is unclear whether the racial disparity in survival is explained by these factors. The objective of this study was to assess racial/ethnic differences in breast cancer survival by inflammatory status and hormone receptor status.Methods
This study examined breast cancer mortality among non-Hispanic white (NHW), Hispanic white, black, and Asian/Pacific Islander (API) women diagnosed between 1990 and 2004 using the National Cancer Institute’s Surveillance, Epidemiology, and End Results data. Kaplan–Meier survival curves and Cox proportional hazard ratios (HRs) assessed the relationship between race/ethnicity and survival.Results
Black women had significantly poorer survival than NHW women regardless of inflammatory status and hormone receptor status. Compared to NHWs, the HRs for black women were 1.32 (95 % confidence interval (CI) 1.21–1.44), 1.43 (95 % CI 1.20–1.69), and 1.30 (95 % CI 1.16–1.47) for IBC, IBC with ER+/PR+, and with ER?/PR?, respectively. Similar HRs were found for non-IBC, non-IBC with ER+/PR?, and non-IBC with ER?/PR?. API women had significantly better survival than NHW women regardless of inflammatory status and hormone receptor status.Conclusion
Compared to NHW women, black women had poorer survival regardless of inflammatory status and hormone receptor status and API women had better survival. These results suggest that factors other than inflammatory status and hormone receptor status may play a role in racial/ethnic disparities in breast cancer survival. 相似文献96.
WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer 下载免费PDF全文
Celina?G?Kleer Yanhong?Zhang Quintin?Pan Gary?Gallagher Mei?Wu Zhi-Fen?Wu Sofia?D?MerajverEmail author 《Breast cancer research : BCR》2003,6(2):R110
Background
Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer. We found concordant and consistent alterations of two genes in 90% of IBC tumors when compared with stage-matched non-IBC tumors: overexpression of RhoC guanosine triphosphatase and loss of WNT-1 induced secreted protein 3 (WISP3). Further work revealed that RhoC is a transforming oncogene for human mammary epithelial (HME) cells. Despite the aggressiveness of the RhoC-driven phenotype, it does not quantitatively reach that of the true IBC tumors. We have demonstrated that WISP3 has tumor growth and angiogenesis inhibitory functions in IBC. We proposed that RhoC and WISP3 cooperate in the development of IBC. 相似文献97.
Yuanyuan Wu Kathryn CB Tan Sammy WM Shiu Yishan Luo Lin Shi Timothy CY Kwok 《Journal of diabetes investigation.》2022,13(11):1873
Aims/IntroductionTo examine the association between cholesterol efflux capacity (CEC) of serum high‐density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus.Materials and MethodsParticipants of a randomized placebo‐controlled trial of 27‐month vitamin B12 supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed. Brain magnetic resonance imaging scans were carried out in a subset at baseline, month 27 and month 45. Fasting serum at baseline, month 9, month 27 and month 72 were analyzed for adenosine triphosphate‐binding cassette transporter A1‐mediated CEC of HDL and apolipoprotein A1 (ApoA1).ResultsSerum HDL cholesterol at baseline was associated with better executive and memory function at follow up. Serum ApoA1 was associated with a better memory Z‐score at month 18. Serum CEC and ApoA1 were not associated with Clinical Dementia Rating scale, Neuropsychological Test Battery, hippocampal volume and white matter disease on magnetic resonance imaging at baseline and whole brain atrophy rates. They were also not associated with cognitive function at month 27 and 72 on multilevel modeling. CEC and ApoA1 decreased significantly from baseline to month 27. Faster decliners in CEC had a greater increase in brain peak width of skeletonized mean diffusivity.ConclusionsHigher serum HDL cholesterol was associated with more favorable changes in memory and executive function in older people with diabetes mellitus. However, this was not due to CEC or ApoA1. A decline in CEC was associated with small vessel disease in the brain. 相似文献
98.
Grant D. Stewart Sarah J. Welsh Stephan Ursprung Ferdia A. Gallagher James O. Jones Jacqui Shields Christopher G. Smith Thomas J. Mitchell Anne Y. Warren Axel Bex Ekaterini Boleti Jade Carruthers Tim Eisen Kate Fife Abdel Hamid Alexander Laird Steve Leung Jahangeer Malik Iosif A. Mendichovszky Faiz Mumtaz Grenville Oades Andrew N. Priest Antony C. P. Riddick Balaji Venugopal Michelle Welsh Kathleen Riddle Lisa E. M. Hopcroft NAXIVA Trial Group Robert J. Jones 《British journal of cancer》2022,127(6):1051
Background Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor.Methods NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity.Results In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype.Conclusions NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery.Clinical trial registration .Subject terms: NCT03494816Surgical oncology, Renal cell carcinoma, Predictive markers 相似文献
99.
Christopher O. Audu William J. Melvin Amrita D. Joshi Sonya J. Wolf Jadie Y. Moon Frank M. Davis Emily C. Barrett Kevin D. Mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam C. Tsoi Sriganesh B. Sharma Tyler M. Bauer James Shadiow Matthew A. Corriere Andrea T. Obi Steven L. Kunkel Benjamin Levi Bethany B. Moore Johann E. Gudjonsson Andrew M. Smith Katherine A. Gallagher 《Cellular & molecular immunology》2022,19(11):1251
100.
Lever R Lo WT Faraidoun M Amin V Brown RA Gallagher J Page CP 《British journal of pharmacology》2007,151(6):837-843
BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions. 相似文献