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991.
Tamara Costas Pedro Besada Alessandro Piras Laura Acevedo Matilde Yañez Francisco Orallo Reyes Laguna Carmen Terán 《Bioorganic & medicinal chemistry letters》2010,20(22):6624-6627
New 6-substituted and 2,6-disubstituted pyridazinone derivatives were obtained starting from easily accessible alkyl furans by using oxidation with singlet oxygen to give 4-methoxy or 4-hydroxybutenolides, key intermediates of this synthetic strategy. The new pyridazinone derivatives have been studied as vasorelaxant and antiplatelet agents. Analysis of biological data revealed the silyl ethers (4a–i) and N,O-dibenzyl derivatives (6g–i) as the most active compounds. 相似文献
992.
Debanu Das Robert D. Finn Polat Abdubek Tamara Astakhova Herbert L. Axelrod Constantina Bakolitsa Xiaohui Cai Dennis Carlton Connie Chen Hsiu‐Ju Chiu Michelle Chiu Thomas Clayton Marc C. Deller Lian Duan Kyle Ellrott Carol L. Farr Julie Feuerhelm Joanna C. Grant Anna Grzechnik Gye Won Han Lukasz Jaroszewski Kevin K. Jin Heath E. Klock Mark W. Knuth Piotr Kozbial S. Sri Krishna Abhinav Kumar Winnie W. Lam David Marciano Mitchell D. Miller Andrew T. Morse Edward Nigoghossian Amanda Nopakun Linda Okach Christina Puckett Ron Reyes Henry J. Tien Christine B. Trame Henry van den Bedem Dana Weekes Tiffany Wooten Qingping Xu Andrew Yeh Jiadong Zhou Keith O. Hodgson John Wooley Marc‐André Elsliger Ashley M. Deacon Adam Godzik Scott A. Lesley Ian A. Wilson 《Protein science : a publication of the Protein Society》2010,19(11):2131-2140
Sufu (Suppressor of Fused), a two‐domain protein, plays a critical role in regulating Hedgehog signaling and is conserved from flies to humans. A few bacterial Sufu‐like proteins have previously been identified based on sequence similarity to the N‐terminal domain of eukaryotic Sufu proteins, but none have been structurally or biochemically characterized and their function in bacteria is unknown. We have determined the crystal structure of a more distantly related Sufu‐like homolog, NGO1391 from Neisseria gonorrhoeae, at 1.4 Å resolution, which provides the first biophysical characterization of a bacterial Sufu‐like protein. The structure revealed a striking similarity to the N‐terminal domain of human Sufu (r.m.s.d. of 2.6 Å over 93% of the NGO1391 protein), despite an extremely low sequence identity of ~15%. Subsequent sequence analysis revealed that NGO1391 defines a new subset of smaller, Sufu‐like proteins that are present in ~200 bacterial species and has resulted in expansion of the SUFU (PF05076) family in Pfam. 相似文献
993.
Christophe Demichelis Johan Oszwald Clélia Gasquet-Blanchard Victor Narat Jean-Christophe Bokika Flora Pennec Tamara Giles-Vernick 《African Journal of Ecology》2020,58(4):692-708
Most landscape cover assessments for conservation programmes rely largely on remote sensing analyses. These analyses, however, neglect how people inhabiting protected zones perceive and structure land cover. Using socio-ecological systems (SES) analysis in a forest-savannah mosaic on the Congo Basin forest edge (Democratic Republic of Congo), we investigated how human practices, landscape perceptions and land use patterns affected forest cover. We conducted remote sensing analysis using a Sentinel-2 satellite image and 187 GPS landmarks, producing a land cover map with 11 classes. Our results yielded an 81.85% correspondence with additional 164 GPS landmarks, a robust score in tropical areas. We conducted 40 individual interviews, eighteen focus group discussion workshops and nine months of participant observation of human practices to identify 19 land units and elaborate a granular SES system structuring the landscape. Integrating local knowledge and practices with general ecological and agronomic processes, we developed a landscape dynamics model revealing progressive forest colonisation of savannahs. Our methods demonstrate that a forest-edge landscape cover evaluation through remote sensing and local knowledge can contribute to finer-grained assessment of land cover and ecosystem services. This assessment can assist conservation efforts by considering local populations' practices on and perceptions of landscape change. 相似文献
994.
Critical land change information enhances the understanding of carbon balance in the United States 总被引:1,自引:0,他引:1
Jinxun Liu Benjamin M. Sleeter Zhiliang Zhu Thomas R. Loveland Terry Sohl Stephen M. Howard Carl H. Key Todd Hawbaker Shuguang Liu Bradley Reed Mark A. Cochrane Linda S. Heath Hong Jiang David T. Price Jing M. Chen Decheng Zhou Norman B. Bliss Tamara Wilson Jason Sherba Qiuan Zhu Yiqi Luo Benjamin Poulter 《Global Change Biology》2020,26(7):3920-3929
Large‐scale terrestrial carbon (C) estimating studies using methods such as atmospheric inversion, biogeochemical modeling, and field inventories have produced different results. The goal of this study was to integrate fine‐scale processes including land use and land cover change into a large‐scale ecosystem framework. We analyzed the terrestrial C budget of the conterminous United States from 1971 to 2015 at 1‐km resolution using an enhanced dynamic global vegetation model and comprehensive land cover change data. Effects of atmospheric CO2 fertilization, nitrogen deposition, climate, wildland fire, harvest, and land use/land cover change (LUCC) were considered. We estimate annual C losses from cropland harvest, forest clearcut and thinning, fire, and LUCC were 436.8, 117.9, 10.5, and 10.4 TgC/year, respectively. C stored in ecosystems increased from 119,494 to 127,157 TgC between 1971 and 2015, indicating a mean annual net C sink of 170.3 TgC/year. Although ecosystem net primary production increased by approximately 12.3 TgC/year, most of it was offset by increased C loss from harvest and natural disturbance and increased ecosystem respiration related to forest aging. As a result, the strength of the overall ecosystem C sink did not increase over time. Our modeled results indicate the conterminous US C sink was about 30% smaller than previous modeling studies, but converged more closely with inventory data. 相似文献
995.
996.
Aleksandra Jauković Tamara Kukolj Hristina Obradović Ivana Okić-Đorđević Slavko Mojsilović Diana Bugarski 《World journal of stem cells》2020,12(9):922-937
Mesenchymal stromal/stem cells(MSCs) are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages. They play a critical role in tissue homeostasis and wound healing, as well as in regulating the inflammatory microenvironment through interactions with immune cells. Hence, MSCs have garnered great attention as promising candidates for tissue regeneration and cell therapy. Because the inflammatory niche plays a key role in triggering the reparative and immunomodulatory functions of MSCs, priming of MSCs with bioactive molecules has been proposed as a way to foster the therapeutic potential of these cells. In this paper, we review how soluble mediators of the inflammatory niche(cytokines and alarmins) influence the regenerative and immunomodulatory capacity of MSCs, highlighting the major advantages and concerns regarding the therapeutic potential of these inflammatory primed MSCs. The data summarized in this review may provide a significant starting point for future research on priming MSCs and establishing standardized methods for the application of preconditioned MSCs in cell therapy. 相似文献
997.
Seo Rin Kim Xiangyu Zou Hui Tang Amrutesh S. Puranik Abdelrhman M. Abumoawad Xiang‐Yang Zhu LaTonya J. Hickson Tamara Tchkonia Stephen C. Textor James L. Kirkland Lilach O. Lerman 《Journal of cellular physiology》2021,236(2):1332-1344
Cell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue‐derived MSCs 2 weeks earlier, or sham. STK senescence‐associated β‐galactosidase (SA‐β‐Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence‐associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue‐derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA‐β‐Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA‐β‐Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS. 相似文献
998.
Background
Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.Objectives
To evaluate the efficacy and safety of rituximab for MS treatment.Data collection
Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.Main results
Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events.Author’s conclusion
Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal. 相似文献999.
Rachel A. Murphy Catherine Schairer Gretchen L. Gierach Celia Byrne Mark E. Sherman Thomas C. Register Jingzhong Ding Stephen B. Kritchevsky Tamara B. Harris 《PloS one》2013,8(10)
Background
Breast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features.Methods
We evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.Results
In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference).Conclusions
These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk. 相似文献1000.
Petr Kohout Tamara Těšitelová Melanie Roy Martin Vohník Jana Jersáková 《Fungal Ecology》2013,6(1):50-64
In addition to orchid mycorrhizal fungi (OrMF), the roots of orchids harbour plant fungal endophytes termed root-associated fungi (RAF). In the present study, the endangered photosynthetic orchid Pseudorchis albida was screened for OrMF and RAF using culture-dependent (isolations from root sections and pelotons) and culture-independent (cloning from root sections) techniques. The efficiency of the different approaches for detecting the fungi and the effect of the sampling season (summer or autumn) were evaluated. In total, 66 distinct OTUs of mycorrhizal and non-mycorrhizal fungi were found, which, to our knowledge, is the highest diversity of RAF that has yet been detected in a single orchid species. The OrMF community was dominated by Tulasnella species, which were mainly detected by isolation from pelotons or cloning from root sections. The roots and tubers showed higher mycorrhizal colonization in summer, corroborating the frequent reports of Tulasnella from pelotons in this season. In contrast, two helotialean fungi, Varicosporium elodeae and Leohumicola sp., the latter of which was repeatedly isolated from pelotons, were significantly more abundant in the autumn. 相似文献