全文获取类型
收费全文 | 473篇 |
免费 | 40篇 |
出版年
2023年 | 3篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 17篇 |
2015年 | 27篇 |
2014年 | 18篇 |
2013年 | 37篇 |
2012年 | 30篇 |
2011年 | 23篇 |
2010年 | 18篇 |
2009年 | 8篇 |
2008年 | 20篇 |
2007年 | 15篇 |
2006年 | 17篇 |
2005年 | 16篇 |
2004年 | 12篇 |
2003年 | 13篇 |
2002年 | 17篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1985年 | 6篇 |
1984年 | 10篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1967年 | 3篇 |
1963年 | 5篇 |
排序方式: 共有513条查询结果,搜索用时 15 毫秒
81.
82.
Urban areas (especially cities) are challenged in meeting their direct water needs from local sources. They also exert strain on global water resources through their indirect (virtual) water use. Agencies concerned with urban water management have visions and goals for managing direct water use, but indirect use is only inferred in more global visions for sustainable consumption. There is limited quantification of “urban water performance” at the macro urban scale (whole of city) to monitor progress toward these goals. It is constrained by a lack of clarity about the evaluation approaches that best serve them. We ask, How can the evaluation approaches described in literature advance urban water management goals? We reviewed the utility of eight evaluation approaches, including urban water system modeling, urban metabolism (territorial and mass balance), consumption (life cycle assessment, water footprinting, and input‐output analysis), and complex systems (ecological network analysis and systems dynamics) approaches. We found that urban metabolism based on water mass balance is a core method for generating information to inform current goals for direct urban water use, with potential for being “coupled” with the other approaches. Consumption approaches inform the management of indirect water use. We describe this in a framework for urban water evaluation to give greater clarity to this field and flag the further research that would be needed to progress this. It includes the recommendation to differentiate the evaluation of direct and indirect urban water, but to also interpret them together. 相似文献
83.
Hamdi F. El-Mowafi Muneera D.F. AlKahtani Mahmoud A. El-Hity Amr M. Reda Latifa Al Husnain E.S. El-Degwy Rizk M. Abdallah Hussah I.M. AlGwaiz A.A. Hadifa Kotb A. Attia 《Saudi Journal of Biological Sciences》2021,28(8):4109-4116
Photoperiod and thermosensitive genetic male sterile (PTGMS) lines have become one of the main sources of global rice production increasing. This study was conducted to evaluate the fertility alteration and validate the male sterility genes using validation markers in novel Egyptian Indica and Japonica PTGMS lines under natural conditions. The study revealed that the new genetic male sterile lines belong to the type of photo–thermosensitive genetic male sterility (PTGMS). The fertility alteration of these lines has influenced by photoperiod and temperature interaction. The new PTGMS lines have three sensitive periods of fertility alteration; transformation, sterility, and fertility period. Furthermore, the sensitive stage of fertility transformation might be from secondary branch primordial to pollen mother cells (PMC) meiosis. Under the natural Sakha condition, the new PTGMS lines were stable sterile under the condition of day length upper 13,75 h and temperature over 25 °C, while its convert to fertile under day length under 13 h, and temperature lower than 24 °C. The co-dominant markers identified the pms3 and tms5 genes in the new PTGMS lines, indicated that the fertility alteration in these lines controlled by photoperiod and thermosensitive stages. 相似文献
84.
Yasmin Silva Rizk Alice Fischer Marillin de Castro Cunha Patrik Oening Rodrigues Maria Carolina Silva Marques Maria de Fátima Cepa Matos M?nica Cristina Toffoli Kadri Carlos Alexandre Carollo Carla Cardozo Pinto de Arruda 《Memórias do Instituto Oswaldo Cruz》2014,109(8):1050-1056
This study is the first phytochemical investigation of Selaginella sellowii
and demonstrates the antileishmanial activity of the hydroethanolic extract
from this plant (SSHE), as well as of the biflavonoids amentoflavone and
robustaflavone, isolated from this species. The effects of these substances were
evaluated on intracellular amastigotes of Leishmania (Leishmania)
amazonensis, an aetiological agent of American cutaneous leishmaniasis.
SSHE was highly active against intracellular amastigotes [the half maximum inhibitory
concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation
of the two bioflavonoids with the highest activity: amentoflavone, which was about
200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and
3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index
(SI) (22 and 30), robustaflavone, which was also active against L.
amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5
µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells.
The production of nitric oxide (NO) was lower in cells treated with amentoflavone
(suggesting that NO does not contribute to the leishmanicidal mechanism in this
case), while NO release was higher after treatment with robustaflavone. S.
sellowii may be a potential source of biflavonoids that could provide
promising compounds for the treatment of cutaneous leishmaniasis. 相似文献
85.
RNA containing 5-fluorouridine (F(5)U) had previously been used to examine the mechanism of the pseudouridine synthase TruA, formerly known as pseudouridine synthase I [Gu et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 14270-14275]. From that work, it was reasonably concluded that the pseudouridine synthases proceed via a mechanism involving a Michael addition by an active site aspartic acid residue to the pyrimidine ring of uridine or F(5)U. Those conclusions rested on the assumption that the hydrate of F(5)U was obtained after digestion of the product RNA and that hydration resulted from hydrolysis of the ester intermediate between the aspartic acid residue and F(5)U. As reported here, (18)O labeling definitively demonstrates that ester hydrolysis does not give rise to the observed hydrated product and that digestion generates not the expected mononucleoside product but rather a dinucleotide between a hydrated isomer of F(5)U and the following nucleoside in RNA. The discovery that digestion products are dinucleotides accounts for the previously puzzling differences in the isolated products obtained following the action of the pseudouridine synthases TruB and RluA on F(5)U in RNA. 相似文献
86.
87.
Yoanne D. Mouwenda Madeleine E. Betouke Ongwe Friederike Sonnet Koen A. Stam Lucja A. Labuda Sophie De Vries Martin P. Grobusch Frejus J. Zinsou Yabo J. Honkpehedji Jean-Claude Dejon Agobe David J. Diemert Remko van Leeuwen Maria E. Bottazzi Peter J. Hotez Peter G. Kremsner Jeffrey M. Bethony Simon P. Jochems Ayola A. Adegnika Marguerite Massinga Loembe Maria Yazdanbakhsh 《PLoS neglected tropical diseases》2021,15(10)
Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov ) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1.In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity. NCT02126462相似文献
88.
89.
Sang Y. Lee Becky Slagle-Webb Elias Rizk Akshal Patel Patti A. Miller Shen-Shu Sung James R. Connor 《PloS one》2014,9(9)
The standard chemotherapy for brain tumors is temozolomide (TMZ), however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer to as CC-I. There is a dose-dependent cytotoxic effect of CC-I in TMZ resistant astrocytoma cells. Cell death appears to occur via apoptosis. Following CC-I exposure, there was an increase in astrocytoma cells in the S and G2/M phases. In in vivo athymic (nu/nu) nude mice subcutaneous and intracranial tumor models, CC-I completely inhibited tumor growth without liver or kidney toxicity. Molecular modeling and enzyme activity assays indicate that CC-I selectively inhibits topoisomerase IIα similar to other drugs in its class, but its cytotoxic effects on astrocytoma cells are stronger than these compounds. The cytotoxic effect of CC-I is stronger in cells expressing unmethylated O6-methylguanine methyltransferase (MGMT) but is still toxic to cells with methylated MGMT. CC-I can also enhance the toxic effect of TMZ on astrocytoma when the two compounds are combined. In conclusion, we have identified a compound that is effective against astrocytomas including TMZ resistant astrocytomas in both cell culture and in vivo brain tumor models. The enhanced cytotoxicity of CC-I and the safety profile of this family of drugs could provide an interesting tool for broader evaluation against brain tumors. 相似文献
90.