全文获取类型
收费全文 | 1938篇 |
免费 | 135篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 49篇 |
妇产科学 | 31篇 |
基础医学 | 232篇 |
口腔科学 | 27篇 |
临床医学 | 276篇 |
内科学 | 365篇 |
皮肤病学 | 43篇 |
神经病学 | 219篇 |
特种医学 | 119篇 |
外科学 | 178篇 |
综合类 | 47篇 |
一般理论 | 3篇 |
预防医学 | 192篇 |
眼科学 | 19篇 |
药学 | 131篇 |
中国医学 | 5篇 |
肿瘤学 | 137篇 |
出版年
2023年 | 14篇 |
2022年 | 44篇 |
2021年 | 79篇 |
2020年 | 44篇 |
2019年 | 69篇 |
2018年 | 64篇 |
2017年 | 43篇 |
2016年 | 43篇 |
2015年 | 56篇 |
2014年 | 57篇 |
2013年 | 100篇 |
2012年 | 84篇 |
2011年 | 106篇 |
2010年 | 37篇 |
2009年 | 57篇 |
2008年 | 84篇 |
2007年 | 62篇 |
2006年 | 71篇 |
2005年 | 53篇 |
2004年 | 68篇 |
2003年 | 65篇 |
2002年 | 56篇 |
2001年 | 42篇 |
2000年 | 49篇 |
1999年 | 32篇 |
1998年 | 24篇 |
1997年 | 30篇 |
1996年 | 24篇 |
1995年 | 24篇 |
1994年 | 15篇 |
1993年 | 14篇 |
1992年 | 39篇 |
1991年 | 23篇 |
1990年 | 38篇 |
1989年 | 46篇 |
1988年 | 29篇 |
1987年 | 26篇 |
1986年 | 27篇 |
1985年 | 36篇 |
1984年 | 23篇 |
1983年 | 14篇 |
1982年 | 13篇 |
1981年 | 16篇 |
1979年 | 10篇 |
1978年 | 11篇 |
1977年 | 18篇 |
1975年 | 11篇 |
1971年 | 9篇 |
1969年 | 8篇 |
1967年 | 9篇 |
排序方式: 共有2079条查询结果,搜索用时 31 毫秒
81.
Nicholas J. Haley Scott Carver Laura L. Hoon-Hanks Davin M. Henderson Kristen A. Davenport Elizabeth Bunting Shawn Gray Bruce Trindle Judith Galeota Ivy LeVan Tracy Dubovos Paul Shelton Edward A. Hoover 《Journal of clinical microbiology》2014,52(9):3237-3243
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic. 相似文献
82.
Brianne A. Couturier Trent Weight Haley Elmer Robert Schlaberg 《Journal of clinical microbiology》2014,52(9):3429-3432
Neonatal Streptococcus agalactiae infections cause significant morbidity and mortality, and antenatal screening is recommended. We compared three U.S. Food and Drug Administration (FDA)-cleared nucleic acid amplification tests (NAATs) to culture using 314 vaginal/rectal swabs after 18 to 24 h (recommended period) and 4 to 8 h (shortened period) of broth enrichment. Agreement of the NAATs with each other was high (97.1% to 98.4%), but culture was less sensitive than all NAATs (67% to 73%). A shortened period of broth culture enrichment resulted in 1 false-negative result in 68 (1.5%). The NAATs performed comparably and were more sensitive than culture. 相似文献
83.
Craig Barnes Binam Bajracharya Matthew Cannalte Zakir Gowani Will Haley Taha Kass-Hout Kyle Hernandez Michael Ingram Hara Prasad Juvvala Gina Kuffel Plamen Martinov J Montgomery Maxwell John McCann Ankit Malhotra Noah Metoki-Shlubsky Chris Meyer Andre Paredes Jawad Qureshi Xenia Ritter Philip Schumm Mingfei Shao Urvi Sheth Trevar Simmons Alexander VanTol Zhenyu Zhang Robert L Grossman 《J Am Med Inform Assoc》2022,29(4):619
ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources. 相似文献
84.
Dan Cojocari Brianna N Smith Julie J. Purkal Maria P. Arrate Jason D. Huska Yu Xiao Agnieszka Gorska Leah J. Hogdal Haley E. Ramsey Erwin R. Boghaert Darren C. Phillips Michael R. Savona 《Haematologica》2022,107(4):825
Dysregulation of apoptotic machinery is one mechanism by which acute myeloid leukemia (AML) acquires a clonal survival advantage. B-cell lymphoma protein-2 (BCL2) overexpression is a common feature in hematologic malignancies. The selective BCL2 inhibitor, venetoclax (VEN) is used in combination with azacitidine (AZA), a DNAmethyltransferase inhibitor (DNMTi), to treat patients with AML. Despite promising response rates to VEN/AZA, resistance to the agent is common. One identified mechanism of resistance is the upregulation of myeloid cell leukemia-1 protein (MCL1). Pevonedistat (PEV), a novel agent that inhibits NEDD8-activating enzyme, and AZA both upregulate NOXA (PMAIP1), a BCL2 family protein that competes with effector molecules at the BH3 binding site of MCL1. We demonstrate that PEV/AZA combination induces NOXA to a greater degree than either PEV or AZA alone, which enhances VEN-mediated apoptosis. Herein, using AML cell lines and primary AML patient samples ex vivo, including in cells with genetic alterations linked to treatment resistance, we demonstrate robust activity of the PEV/VEN/AZA triplet. These findings were corroborated in preclinical systemic engrafted models of AML. Collectively, these results provide rational for combining PEV/VEN/AZA as a novel therapeutic approach in overcoming AML resistance in current therapies. 相似文献
85.
Alex Buga Gary L. Welton Katie E. Scott Adam D. Atwell Sarah J. Haley Noah J. Esbenshade Jacqueline Abraham Jeffrey D. Buxton Dana L. Ault Amy S. Raabe Timothy D. Noakes Parker N. Hyde Jeff S. Volek Philip J. Prins 《Nutrients》2022,14(6)
A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored. 相似文献
86.
Jeanna Wallenta Law Debanjali Mitra Henry G. Kaplan Tamuno Alfred Adam M. Brufsky Birol Emir Haley McCracken Xianchen Liu Ronda G. Broome Chenan Zhang Caroline DiCristo Connie Chen 《Current oncology (Toronto, Ont.)》2022,29(2):1047
This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC. 相似文献
87.
Hazel A. Fargher Russell A. Nickels Thaís P. de Faria Michael M. Haley Michael D. Pluth Darren W. Johnson 《RSC advances》2021,11(43):26581
We highlight a convenient synthesis to selectively deuterate an aryl C–H hydrogen bond donor in an arylethynyl bisurea supramolecular anion receptor and use the Perrin method of competitive titrations to study the deuterium equilibrium isotope effects (DEIE) of anion binding for HS−, Cl−, and Br−. This work highlights the utility and also challenges in using this method to determine EIE with highly reactive and/or weakly binding anions.We highlight a convenient synthesis to selectively deuterate an aryl C–H hydrogen bond donor in a supramolecular anion receptor and use competitive titrations to study the deuterium equilibrium isotope effects (DEIE) in binding HS−, Cl−, and Br−.Molecular recognition and host–guest binding in both biological and synthetic systems are often driven by a mixture of competitive and additive primarily non-covalent interactions. Understanding the role of each of these forces in a host–guest system can reveal insights into the driving forces behind binding and help inform on the molecular design of future hosts.1–3 Equilibrium isotope effects (EIE), also referred to as binding isotope effects (BIE) in structural molecular biology,4 measure the effect of isotopic substitution on supramolecular interactions through changes in the vibrational energy of the substituted bond. These studies can be used to elucidate the complex non-covalent forces involved in host conformational changes and host–guest binding.5–8Examples from structural molecular biology have demonstrated that EIEs can reveal mechanistic information in enzyme–ligand binding events.4,9 Isotopic substitution in synthetic supramolecular systems has been used both for labelling purposes and for studying individual non-covalent interactions. For example, Bergman, Raymond, and coworkers used deuterium equilibrium isotope effects (DEIE) to study benzylphosphonium cation guest binding in a self-assembled supramolecular complex in aqueous solution.10 From these DEIE studies, the authors found that attractive cation⋯π interactions in the interior of the host were important for promoting guest binding, and that C–H⋯π and π⋯π interactions were relatively small contributors. In another example, Shimizu and coworkers studied the DEIE on the strength of C–H⋯π interactions in their molecular balances.11 Both computational and experimental results showed that the strength of C–H⋯π and C–D⋯π interactions were about equal, settling the debate on which interaction is stronger and easing concerns about using deuteration for spectroscopic and labelling applications.Previously, we used DEIE to study Cl− binding with the arylethynyl bisurea anion receptor 1H/D (Fig. 1) in DMSO-d6.12 We found an experimental DEIE of 1.019 ± 0.010, which matched the computationally-predicted DEIE of 1.020. Further computational analysis determined that the DEIE was due to a distorted N–H⋯Cl− hydrogen bond geometry, which resulted in changes in the C–H/D bond vibrational energy in the host–guest complex. In addition, Paneth and coworkers performed a computational study with 1H and other hydrogen bonding supramolecular Cl− receptors to determine the EIE of 35/37Cl− binding in these hosts.13 Because isotope effects, both equilibrium and kinetic, originate solely from changes in the vibrational energy of the isotopically labelled bond, the EIE arising from this study came from changes in the vibrational energies of the bonds in the supramolecular hosts when participating in hydrogen bonding with Cl− isotopes. Indeed, a linear relationship was observed between the hydrogen bond donor (D) D–H bond lengths in the host–guest complex and the computed 35/37Cl EIE.Open in a separate windowFig. 1Arylethynyl bisurea receptors 1H and 1D used in our previous DEIE study of Cl− binding. Related receptors 2H and 2D are used in this study to avoid reaction of the nitro group with HS−.Previous EIE studies with receptor 1H/D have focused on Cl− binding; however, to the best of our knowledge, no work has yet investigated the EIE of hydrosulfide (HS−) binding in this or other systems. HS− is a highly reactive anion that plays crucial roles in biology. At physiological pH, HS− is favored in solution by a 3 : 1 ratio over its conjugate acid, hydrogen sulfide (H2S). H2S has been identified as the third physiological gasotransmitter alongside CO and NO and plays essential roles in physiological systems.15 Despite its high nucleophilicity and redox activity, HS− has been observed to be bound through non-covalent interactions in the protein crystal structure of a bacterial ion channel16 and in the turn-over state of vanadium-containing nitrogenase.17 The supramolecular chemistry of HS− is under-studied in synthetic supramolecular receptors, likely due to the inherent high reactivity of HS−. Indeed, we are aware of only three families of receptors that have been shown to reversibly bind HS−.18–21Recently, we used a series of arylethynyl bisurea anion receptors to investigate and demonstrate a linear free energy relationship between the polarity of a non-traditional C–H hydrogen bond donor and the solution binding energy of HS−, HSe−, Cl− and Br−.14 A major and unexpected finding of this study was that HS− demonstrated a significant increase in sensitivity towards the polarity of the C–H hydrogen donor over HSe−, Cl− and Br−. Although increasing the polarity of the C–H hydrogen bond donor did not lead to changes in selectivity between Cl−, Br−, and HSe−, we observed a 9-fold increase in selectivity for HS− over Cl−, suggesting a fresh approach to selective HS− recognition using non-covalent interactions. In this current study, we label the C–H hydrogen bond donor in an arylethynyl bisurea receptor with a deuterium atom (2H/D, Fig. 1) to further investigate this apparent preference of polar C–H H-bond donors for HS− over Cl− and Br− through DEIE.Receptor 2H is a previously reported anion receptor for HS−, Cl−, and Br− and was prepared by established methods.14 Deuterium labelling of the isotopologue 2D was achieved by selective monodeuteration of intermediates through methods similar to those reported in the literature (Scheme 1).22 The diazonium salt 3 was synthesized in a 71% yield from 2,6-diiodo-4-trifluoromethylaniline.23 Dediazonation in DMF-d7 is catalyzed by FeSO4 and allows for selective synthesis of monodeuterated intermediate 4. The deuteration step proceeds through a radical pathway that uses DMF-d7 as the deuterium source. This deuteration reaction provides efficient deuterium incorporation even with up to 50% by volume H2O in the reaction solution due to the differential bond strengths in DMF and H2O.22 Sonogashira cross-coupling reaction of 4 and 4-t-butyl-2-ethynylaniline24 afforded 5 in 45% yield. Subsequent addition with 4-methoxyphenyl isocyanate gave 2D in 34% yield. Compound 2D and intermediates were characterized through 1H, 2H, 13C{1H}, and 19F NMR spectroscopy and high-resolution mass spectrometry (see ESI†).Open in a separate windowScheme 1Synthetic route for the selective deuteration of anion receptor 2D.Previous work on the DEIE of Cl− binding with 1H/D in DMSO revealed an experimental isotope effect of 1.019 ± 0.010. Therefore, we expected similar small DEIEs for HS−, Cl−, and Br− binding with 2H/D. Typical methods to determine binding constants (Ka) in supramolecular systems use non-linear regression fitting of titration data. Results from this method can be affected by small errors in the known initial host and guest concentration, quality of the titration isotherm, and subsequent data fitting, which when taken together often results in 2–15% errors in Ka. To increase the precision in KHa/KDa data for this study, we used the Perrin method of competitive titrations,25 which has been shown previously to reduce errors in EIE values significantly with errors as small as 0.0004.26 In this method, a linearized plot of the chemical shifts of 2H (δH) and 2D (δD) in fast exchange with an anionic guest is fit by linear regression to eqn (1):(δ0H − δH)(δD − δfD) = DEIE(δ0D − δD)(δH − δfH)1The slope of the linear regression is equal to the DEIE of the system. Because the linear regression only relies on chemical shift values and is independent of host and guest concentration, the precision of the method is limited to the precision of the NMR instrument and quality of data fitting.In addition, 13C NMR spectroscopy is sensitive to isotopic labelling and can show changes in chemical shifts between isotopomers. We were able to differentiate between the 13C NMR signals for Cab, C1 and C2 for free and bound 2H and 2D (Fig. 2a) in 10% DMSO-d6/CD3CN, which were similar to those reported for 1H/D in DMSO-d6.12 Competitive 13C NMR spectroscopy titrations were performed in anaerobic and anhydrous 10% DMSO-d6/CD3CN at 25 °C with mixtures of 2H and 2D in combined concentrations between 5.71 and 13.46 mM. Aliquots of the tetrabutylammonium (TBA) salts of HS−, Cl−, and Br− were added until the system had reached saturation (Titration method A in ESI†). In an effort to decrease reactivity of HS− with 2H/D and DMSO over long periods of time and decrease oxygen and water contaminations, some titrations with HS− were performed by splitting the host solution of 2H/D between four J-young NMR tubes. For each point in the competitive titration, TBASH was added to a new solution of 2H/D inside an N2-filled glovebox shortly before obtaining a 13C NMR spectra (Titration method B in ESI†). The Cab, C1 and C2 13C NMR signals were tracked for 2H and 2D in each titration for each anion. A representative competitive titration and linearized plots for Cl− binding is shown in Fig. 2.Open in a separate windowFig. 2(a) Representation of the host–guest equilibrium between 2H/D and Cl−. (b) Differences in the chemical shifts between the 2H and 2D isotopologues are observed in the 13C NMR signals for the Cab, C1, and C2 carbons. 13C NMR signals for the Cab, C1, and C2 carbons in 2H and 2D are tracked throughout a titration. (c–e) Linearized plots from fitting the chemical shifts of the Cab, C1, and C2 throughout a titration to eqn (1).The DEIE data calculated from tracking the chemical shifts of the Cab, C1 and C2 13C NMR signals from Cl− and Br− binding are summarized in eqn (1) through linear regression is included in parentheses
Open in a separate windowNotably, our experimental DEIE value for Cl− binding with 2H/D in 10% DMSO-d6/CD3CN is smaller than the computed value of 1.020 for Cl− binding with 1H/D in DMSO-d6.12 Our previously published computational study revealed that the DEIE of Cl− binding resulted from distorted urea N–H⋯Cl− hydrogen bonding geometry affecting the vibrational frequency of the C–H/D bond in the host–guest complex. Replacing the NO2 functional group in 1H/D (σp = 0.78) with a CF3 functional group (σp = 0.54) in 2H/D decreases the polarization of the C–H/D bond and subsequently makes it a slightly poorer hydrogen bond donor. In addition, the DEIE of Cl− binding in this current study is in a less polar solvent system (10% DMSO/CH3CN, ε ∼ 42) compared to the previous study (DMSO, ε = 47). We hypothesize that the decreased polarization of the C–H/D bond and the lower solvent polarity either relieve the distorted N–H⋯Cl− hydrogen bonding geometry or decrease their influence on the vibrational frequency of the C–H/D bond in the host–guest complex. To deconvolute and better understand the role of both C–H/D hydrogen bond donor polarity and solvent on the DEIE of Cl− binding in these receptors, a systematic study of these two variables would be required, similar to those previously reported, which we intend to pursue in future work.14,27,28Analysis of the data for competitive titrations of 2H/D with Br− revealed no DEIE at any of the tracked 13C NMR signals; however, each calculated DEIE has a relatively large percent error (0.99–4.64%, compared to 0.20% for the DEIE of Cl− binding), which could potentially obscure small DEIEs. We attribute these large percent errors to a limitation in the Perrin method that assumes that the hosts are fully bound by guest at saturation. This limitation can potentially decrease the precision of this method for weakly bound guests with low Ka, such as Br− which has a Ka of 173 ± 9 M−1 with 2H in 10% DMSO-d6/CD3CN at 25 °C.14Using the combined data from 11 experiments, we were unable to determine a DEIE for HS− binding. The C1 13C NMR signal appeared to be the most sensitive to the change in vibrational energy of the C–H/D bond in the free host and the host–guest complex; however, in over half these trials, data from the C1 13C NMR signal showed a poor linear fit (R2 < 0.99). In addition, we were unable to triplicate any DEIE from the data which showed a good linear fit (R2 > 0.99). We hypothesize that the high nucleophilicity and air and water sensitivity of HS− made it incompatible with the long experiment times needed for 13C NMR spectroscopy titrations. In addition it is important to note that HS− is the only protic guest investigated in these studies, and it is also possible that vibrational coupling between the S–H motif and the receptor may further complicate the measurement of these small EIEs. Such coupling between S–H and other motifs has been implicated previously in the IR inactivity of S–H stretching modes in many metal-sulfhydryl complexes.29In conclusion, deuterium equilibrium isotope effects (DEIE) can be used to elucidate non-covalent driving forces behind anion binding in our arylethynyl bisurea receptors. We endeavored to use DEIE studies to further investigate a preference of polarized C–H hydrogen bond donors for HS− over Cl− and Br− which we reported previously.14 In this current work, we highlight a convenient method to selectively and completely deuterate the aryl C–H hydrogen bond donor in our supramolecular anion receptors. We then found a DEIE of 1.014 ± 0.002 for Cl− binding with 2H/D. This DEIE was smaller than the computed DEIE of Cl− binding with 1H/D which features a more polarized C–H hydrogen bond donor and in a more polar solvent. Finally, we reveal challenges in using the Perrin method and 13C NMR spectroscopy titrations in determining small and precise EIE for weakly binding or highly reactive guests.From this work, we have identified several areas that need further research. The first is to study how solvent and hydrogen bond donor polarity affect EIE of guest binding. A computational study from Paneth and coworkers suggest that both these variables can be used to influence 35/37Cl EIE in supramolecular hosts.13 We also were unable to determine a DEIE of HS− binding in our receptors, likely due to its high reactivity. A new method to determine small, precise EIE of reactive species such as HS− is needed in order to learn more about the supramolecular chemistry of this biologically relevant anion and to develop new strategies for selectively binding HS− over other competing anions. 相似文献
13C NMR Signal | DEIE (R2) | |
---|---|---|
Carbon | Cl− | Br− |
Cab | 0.983 ± 0.017 (0.997) | 1.006 ± 0.010 (0.999) |
C1 | 1.006 ± 0.007 (0.999) | 1.009 ± 0.018 (0.997) |
C1 | 1.014 ± 0.002 (1.00) | 0.990 ± 0.046 (0.981) |
88.
89.
90.
uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues 总被引:10,自引:0,他引:10
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Meng S Tripathy D Shete S Ashfaq R Saboorian H Haley B Frenkel E Euhus D Leitch M Osborne C Clifford E Perkins S Beitsch P Khan A Morrison L Herlyn D Terstappen LW Lane N Wang J Uhr J 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(46):17361-17365
Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively. 相似文献