全文获取类型
收费全文 | 742篇 |
免费 | 36篇 |
出版年
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 23篇 |
2012年 | 35篇 |
2011年 | 32篇 |
2010年 | 13篇 |
2009年 | 17篇 |
2008年 | 26篇 |
2007年 | 23篇 |
2006年 | 41篇 |
2005年 | 46篇 |
2004年 | 26篇 |
2003年 | 34篇 |
2002年 | 54篇 |
2001年 | 59篇 |
2000年 | 46篇 |
1999年 | 31篇 |
1998年 | 17篇 |
1997年 | 8篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 15篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 10篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 7篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1969年 | 4篇 |
排序方式: 共有778条查询结果,搜索用时 46 毫秒
31.
A simple analysis was developed to compare granulocyte production in marrow with granulocyte turnover in peripheral blood of the dog. the analysis is anchored to the relative number of granulopoietic and erythropoietic cells that are flashlabeled with tritiated thymidine. This provides a convenient measure of relative production rates, since there is little, if any, difference in the duration of the respective DNA synthesis periods. the latter was confirmed in the present work by comparison of myeloid and erythroid cells in respect to (1) labeled mitosis curves and (2) changes in labeling intensity with constant infusion of tritiated thymidine. the ratio of flash-labeled granulocyte to erythrocyte progenitors was unity (1.02 ± 0.05) in the eight dogs studied, which means that gross production rates were essentially the same. Since net production as revealed by peripheral blood turnover is greater for erythrocytes than for granulocytes, it follows that there must be some ineffective granulopoiesis. This may correspond to over half of the total production. It is suggested that this phenomenon, which apparently occurs in man as well as in dog, could represent an important feature of granulocyte regulation. 相似文献
32.
Kelly O. Maloney Kevin P. Krause Claire Buchanan Lauren E. Hay Gregory J. McCabe Zachary M. Smith Terry L. Sohl John A. Young 《Global Change Biology》2020,26(4):2251-2269
Land‐use and climate change are significantly affecting stream ecosystems, yet understanding of their long‐term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land‐use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin‐wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land‐use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) and a watershed‐wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land‐use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed‐wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land‐use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed‐wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%–26.2% of stream kilometers, dependent on land‐use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land‐use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions. 相似文献
33.
34.
Kathleen M. Maloney Jenny Ancca‐Juarez Renzo Salazar Katty Borrini‐Mayori Malwina Niemierko Joshua O. Yukich Cesar Naquira Joseph A. Keating Michael Z. Levy 《Journal of vector ecology》2013,38(1):6-11
The vector of Chagas disease, Triatoma infestans, is largely controlled by the household application of pyrethroid insecticides. Because effective, large‐scale insecticide application is costly and necessitates numerous trained personnel, alternative control techniques are badly needed. We compared the residual effect of organophosphate‐based insecticidal paint (Inesfly 5A IGR? (I5A)) to standard deltamethrin, and a negative control, against T. infestans in a simulated natural environment. We evaluated mortality, knockdown, and ability to take a blood meal among 5th instar nymphs. I5A paint caused significantly greater mortality at time points up to nine months compared to deltamethrin (Fisher's Exact Test, p < 0.01 in all instances). A year following application, mortality among nymphs in the I5A was similar to those in the deltamethrin (χ2 = 0.76, df=1, p < 0.76). At months 0 and 1 after application, fewer nymphs exposed to deltamethrin took a blood meal compared to insects exposed to paint (Fisher's Exact Tests, p < 0.01 and p < 0.01, respectively). Insecticidal paint may provide an easily‐applied means of protection against vectors of Chagas disease. 相似文献
35.
Julia Rhodes Surang Dejsirilert Susan A. Maloney Possawat Jorakate Anek Kaewpan Prasert Salika Thantapat Akarachotpong Prabda Prapasiri Sathapana Naorat Peera Areerat Asadang Ruayajin Pathom Sawanpanyalert Pasakorn Akarasewi Leonard F. Peruski Jr Henry C. Baggett 《PloS one》2013,8(6)
Background
Streptococcus pneumoniae is an important cause of morbidity and mortality in Southeast Asia, but regional data is limited. Updated burden estimates are critical as pneumococcal conjugate vaccine (PCV) is highly effective, but not yet included in the Expanded Program on Immunization of Thailand or neighboring countries.Methods
We implemented automated blood culture systems in two rural Thailand provinces as part of population-based surveillance for bacteremia. Blood cultures were collected from hospitalized patients as clinically indicated.Results
From May 2005– March 2010, 196 cases of pneumococcal bacteremia were confirmed in hospitalized patients. Of these, 57% had clinical pneumonia, 20% required mechanical ventilation, and 23% (n = 46) died. Antibiotic use before blood culture was confirmed in 25% of those with blood culture. Annual incidence of hospitalized pneumococcal bacteremia was 3.6 per 100,000 person-years; rates were higher among children aged <5 years at 11.7 and adults ≥65 years at 14.2, and highest among infants <1 year at 33.8. The median monthly case count was higher during December–March compared to the rest of the year 6.0 vs. 1.0 (p<0.001). The most common serotypes were 23F (16%) and 14 (14%); 61% (74% in patients <5 years) were serotypes in the 10-valent PCV (PCV 10) and 82% (92% in <5 years) in PCV 13. All isolates were sensitive to penicillin, but non-susceptibility was high for co-trimoxazole (57%), erythromycin (30%), and clindamycin (20%).Conclusions
We demonstrated a high pneumococcal bacteremia burden, yet underestimated incidence because we captured only hospitalized cases, and because pre-culture antibiotics were frequently used. Our findings together with prior research indicate that PCV would likely have high serotype coverage in Thailand. These findings will complement ongoing cost effectiveness analyses and support vaccine policy evaluation in Thailand and the region. 相似文献36.
Tenzin Gayden Annabel Perez Patrice J. Persad Areej Bukhari Shilpa Chennakrishnaiah Tanya Simms Trisha Maloney Kristina Rodriguez Rene J. Herrera 《American journal of physical anthropology》2013,151(2):169-182
The Himalayan mountain range is strategically located at the crossroads of the major cultural centers in Asia, the Middle East and Europe. Although previous Y‐chromosome studies indicate that the Himalayas served as a natural barrier for gene flow from the south to the Tibetan plateau, this region is believed to have played an important role as a corridor for human migrations between East and West Eurasia along the ancient Silk Road. To evaluate the effects of the Himalayan mountain range in shaping the maternal lineages of populations residing on either side of the cordillera, we analyzed mitochondrial DNA variation in 344 samples from three Nepalese collections (Newar, Kathmandu and Tamang) and a general population of Tibet. Our results revealed a predominantly East Asian‐specific component in Tibet and Tamang, whereas Newar and Kathmandu are both characterized by a combination of East and South Central Asian lineages. Interestingly, Newar and Kathmandu harbor several deep‐rooted Indian lineages, including M2, R5, and U2, whose coalescent times from this study (U2, >40 kya) and previous reports (M2 and R5, >50 kya) suggest that Nepal was inhabited during the initial peopling of South Central Asia. Comparisons with our previous Y‐chromosome data indicate sex‐biased migrations in Tamang and a founder effect and/or genetic drift in Tamang and Newar. Altogether, our results confirm that while the Himalayas acted as a geographic barrier for human movement from the Indian subcontinent to the Tibetan highland, it also served as a conduit for gene flow between Central and East Asia. Am J Phys Anthropol 151:169–182, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
37.
Mark J. Mitton-Fry Steven J. Brickner Judith C. Hamel Lori Brennan Jeffrey M. Casavant Michael Chen Tao Chen Xiaoyuan Ding James Driscoll Joel Hardink Thuy Hoang Erbing Hua Michael D. Huband Meghan Maloney Anthony Marfat Sandra P. McCurdy Dale McLeod Michael Plotkin Christopher Zook 《Bioorganic & medicinal chemistry letters》2013,23(10):2955-2961
A structurally novel set of inhibitors of bacterial type II topoisomerases with potent in vitro and in vivo antibacterial activity was developed. Dual-targeting ability, hERG inhibition, and pharmacokinetic properties were also assessed. 相似文献
38.
Andrew S. Rosenthal Thomas S. Dexheimer Opher Gileadi Giang H. Nguyen Wai Kit Chu Ian D. Hickson Ajit Jadhav Anton Simeonov David J. Maloney 《Bioorganic & medicinal chemistry letters》2013,23(20):5660-5666
Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome. 相似文献
39.
Natalia J. Martinez Ganesha Rai Adam Yasgar Wendy A. Lea Hongmao Sun Yuhong Wang Diane K. Luci Shyh-Ming Yang Kana Nishihara Shunichi Takeda Mohiuddin Irina Earnshaw Tetsuya Okada Kazutoshi Mori Kelli Wilson Gregory J. Riggins Menghang Xia Maurizio Grimaldi Ajit Jadhav David J. Maloney Anton Simeonov 《PloS one》2016,11(11)
40.
Shyh-Ming Yang Makoto Yoshioka Jeffrey W. Strovel Daniel J. Urban Xin Hu Matthew D. Hall Ajit Jadhav David J. Maloney 《Bioorganic & medicinal chemistry letters》2019,29(10):1220-1226
Extensive optimization of quinazoline-based lead 8 is described. The structure-activity relationship studies indicate the S-configuration is preferred for the phenylmorpholine substitution. Together with incorporation of a (2-hydroxyl-2-methylpropyl)pyrazole moiety at the 2-position leads to analogs with comparable potency and marked improvement in the pharmacokinetic profile over our previously reported lead compounds. Further in vivo efficacy studies in Kasumi-1 xenograft mouse model demonstrates that the selected inhibitors are well tolerated and highly efficacious in the inhibition of tumor growth. Additionally, the representative analog 19 also demonstrated significant improvement of arthritis severity in a collagen-induced arthritis (CIA) mouse model. These results indicate potential use of these quinazoline-based BET inhibitors for treatment of cancer and inflammatory diseases. A brief discussion of the co-crystallized structure of 19 with BRD4 (BD1) is also highlighted. 相似文献