全文获取类型
收费全文 | 1525篇 |
免费 | 61篇 |
出版年
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 16篇 |
2019年 | 7篇 |
2018年 | 16篇 |
2017年 | 22篇 |
2016年 | 38篇 |
2015年 | 48篇 |
2014年 | 46篇 |
2013年 | 72篇 |
2012年 | 86篇 |
2011年 | 91篇 |
2010年 | 41篇 |
2009年 | 56篇 |
2008年 | 83篇 |
2007年 | 95篇 |
2006年 | 74篇 |
2005年 | 77篇 |
2004年 | 76篇 |
2003年 | 82篇 |
2002年 | 76篇 |
2001年 | 49篇 |
2000年 | 43篇 |
1999年 | 28篇 |
1998年 | 24篇 |
1997年 | 16篇 |
1996年 | 12篇 |
1995年 | 14篇 |
1994年 | 9篇 |
1993年 | 13篇 |
1992年 | 24篇 |
1991年 | 20篇 |
1990年 | 25篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 17篇 |
1984年 | 14篇 |
1983年 | 13篇 |
1982年 | 7篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1974年 | 15篇 |
1973年 | 7篇 |
1971年 | 8篇 |
1969年 | 7篇 |
1967年 | 5篇 |
排序方式: 共有1586条查询结果,搜索用时 31 毫秒
951.
Entomopathogenic fungi, such as Metarhizium anisopliae (Metch.) Sorokin, are important agents for the biological control of insect pests. However, these fungi are not compatible with high temperatures. In this study, mutagenesis using ion beams or gamma rays was used to generate five potentially thermotolerant mutants from two wild-type isolates of M. anisopliae (two using ion beams and three using gamma rays). The mutant isolates had a higher upper thermal limit for vegetative growth compared to the wild types (by 2–3°C) and enhanced tolerance to wet–heat stress of 45°C for conidial germination. At 25°C and 30°C, most mutants were as virulent to maize weevil adults as the wild type, however, one mutant produced using ion beams almost lost virulence entirely. These results indicate that ion beams and gamma rays are useful tools for improving biological characteristics, such as thermotolerance, in entomopathogenic fungi, but that mutants must be carefully evaluated for unpredictable negative side effects. 相似文献
952.
Tatsuya Amano Brody Sandel Heidi Eager Edouard Bulteau Jens-Christian Svenning Bo Dalsgaard Carsten Rahbek Richard G. Davies William J. Sutherland 《Proceedings. Biological sciences / The Royal Society》2014,281(1793)
Many of the world''s languages face serious risk of extinction. Efforts to prevent this cultural loss are severely constrained by a poor understanding of the geographical patterns and drivers of extinction risk. We quantify the global distribution of language extinction risk—represented by small range and speaker population sizes and rapid declines in the number of speakers—and identify the underlying environmental and socioeconomic drivers. We show that both small range and speaker population sizes are associated with rapid declines in speaker numbers, causing 25% of existing languages to be threatened based on criteria used for species. Language range and population sizes are small in tropical and arctic regions, particularly in areas with high rainfall, high topographic heterogeneity and/or rapidly growing human populations. By contrast, recent speaker declines have mainly occurred at high latitudes and are strongly linked to high economic growth. Threatened languages are numerous in the tropics, the Himalayas and northwestern North America. These results indicate that small-population languages remaining in economically developed regions are seriously threatened by continued speaker declines. However, risks of future language losses are especially high in the tropics and in the Himalayas, as these regions harbour many small-population languages and are undergoing rapid economic growth. 相似文献
953.
Nancy Ockendon David J. Baker Jamie A. Carr Elizabeth C. White Rosamunde E. A. Almond Tatsuya Amano Esther Bertram Richard B. Bradbury Cassie Bradley Stuart H. M. Butchart Nathalie Doswald Wendy Foden David J. C. Gill Rhys E. Green William J. Sutherland Edmund V. J. Tanner James W. Pearce‐Higgins 《Global Change Biology》2014,20(7):2221-2229
Shifts in species' distribution and abundance in response to climate change have been well documented, but the underpinning processes are still poorly understood. We present the results of a systematic literature review and meta‐analysis investigating the frequency and importance of different mechanisms by which climate has impacted natural populations. Most studies were from temperate latitudes of North America and Europe; almost half investigated bird populations. We found significantly greater support for indirect, biotic mechanisms than direct, abiotic mechanisms as mediators of the impact of climate on populations. In addition, biotic effects tended to have greater support than abiotic factors in studies of species from higher trophic levels. For primary consumers, the impact of climate was equally mediated by biotic and abiotic mechanisms, whereas for higher level consumers the mechanisms were most frequently biotic, such as predation or food availability. Biotic mechanisms were more frequently supported in studies that reported a directional trend in climate than in studies with no such climatic change, although sample sizes for this comparison were small. We call for more mechanistic studies of climate change impacts on populations, particularly in tropical systems. 相似文献
954.
Hirotada Akiho Yohei Tokita Kazuhiko Nakamura Kazuko Satoh Mitsue Nishiyama Naoko Tsuchiya Kazuaki Tsuchiya Katsuya Ohbuchi Yoichiro Iwakura Eikichi Ihara Ryoichi Takayanagi Masahiro Yamamoto 《PloS one》2014,9(5)
Background and Aim
The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown, however, a possible involvement of T cells is suggested.Methods
Using the mouse model of T cell activation-induced enteritis, we investigated whether enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A is involved in postinflammatory GI hypermotility.Results
Activation of CD3 induces temporal enteritis with GI hypomotility in the midst of, and hypermotility after resolution of, intestinal inflammation. Prolonged upregulation of IL-17A was prominent and IL-17A injection directly enhanced GI transit and contractility of intestinal strips. Postinflammatory hypermotility was not observed in IL-17A-deficient mice. Incubation of a muscle strip and SMCs with IL-17A in vitro resulted in enhanced contractility with increased phosphorylation of Ser19 in myosin light chain 2 (p-MLC), a surrogate marker as well as a critical mechanistic factor of SMC contractility. Using primary cultured murine and human intestinal SMCs, IκBζ- and p38 mitogen-activated protein kinase (p38MAPK)-mediated downregulation of the regulator of G protein signaling 4 (RGS4), which suppresses muscarinic signaling of contraction by promoting inactivation/desensitization of Gαq/11 protein, has been suggested to be involved in IL-17A-induced hypercontractility. The opposite effect of L-1β was mediated by IκBζ and c-jun N-terminal kinase (JNK) activation.Conclusions
We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders. 相似文献955.
956.
Ryoko Sakai Soo-Kyung Cho Toshihiro Nanki Kaori Watanabe Hayato Yamazaki Michi Tanaka Ryuji Koike Yoshiya Tanaka Kazuyoshi Saito Shintaro Hirata Koichi Amano Hayato Nagasawa Takayuki Sumida Taichi Hayashi Takahiko Sugihara Hiroaki Dobashi Shinsuke Yasuda Tetsuji Sawada Kazuhiko Ezawa Atsuhisa Ueda Takao Fujii Kiyoshi Migita Nobuyuki Miyasaka Masayoshi Harigai for the REAL Study Group 《Arthritis research & therapy》2015,17(1)
IntroductionThe objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice.MethodsThis prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry. We assessed types and incidence rates (IRs) of serious adverse events (SAEs) and serious infections (SIs) during the first year of treatment. Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis.ResultsPatients in the TCZ group had longer disease duration (P <0.001), higher disease activity (P = 0.019) and more frequently used concomitant corticosteroids (P <0.001) than those in the TNFI group. The crude IR (/100 PY) of SIs [TCZ 10.68 vs. TNFI 3.03; IR ratio (95% confidence interval [CI]), 3.53 (1.52 to 8.18)], but not SAEs [21.36 vs. 14.72; 1.45 (0.94 to 2.25)], was significantly higher in the TCZ group compared with the TNFI group. However, after adjusting for covariates using the Cox regression hazard analysis, treatment with TCZ was not associated with higher risk for SAEs [hazard ratio (HR) 1.28, 95% CI 0.75 to 2.19] or SIs (HR 2.23, 95% CI 0.93 to 5.37).ConclusionsThe adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs, indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0583-8) contains supplementary material, which is available to authorized users. 相似文献957.
Susan I. Jarvi William C. Pitt Margaret E. Farias Laura Shiels Michael G. Severino Kathleen M. Howe Steven H. Jacquier Aaron B. Shiels Karis K. Amano Blaine C. Luiz Daisy E. Maher Maureen L. Allison Zachariah C. Holtquist Neil T. Scheibelhut 《PloS one》2015,10(4)
The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes human eosinophilic meningitis and ocular angiostrongyliasis characteristic of rat lungworm (RLW) disease. Definitive diagnosis is made by finding and identifying A. cantonensis larvae in the cerebral spinal fluid or by using a custom immunological or molecular test. This study was conducted to determine if genomic DNA from A. cantonensis is detectable by qPCR in the blood or tissues of experimentally infected rats. F1 offspring from wild rats were subjected to experimental infection with RLW larvae isolated from slugs, then blood or tissue samples were collected over multiple time points. Blood samples were collected from 21 rats throughout the course of two trials (15 rats in Trial I, and 6 rats in Trial II). In addition to a control group, each trial had two treatment groups: the rats in the low dose (LD) group were infected by approximately 10 larvae and the rats in the high dose (HD) group were infected with approximately 50 larvae. In Trial I, parasite DNA was detected in cardiac bleed samples from five of five LD rats and five of five HD rats at six weeks post-infection (PI), and three of five LD rats and five of five HD rats from tail tissue. In Trial II, parasite DNA was detected in peripheral blood samples from one of two HD rats at 53 minutes PI, one of two LD rats at 1.5 hours PI, one of two HD rats at 18 hours PI, one of two LD rats at five weeks PI and two of two at six weeks PI, and two of two HD rats at weeks five and six PI. These data demonstrate that parasite DNA can be detected in peripheral blood at various time points throughout RLW infection in rats. 相似文献
958.
Tetsuya Toyono Tomohiko Usui Seiichi Yokoo Yukako Taketani Suguru Nakagawa Masahiko Kuroda Satoru Yamagami Shiro Amano 《PloS one》2015,10(1)
Purpose
We sought to identify the anti-angiogenic molecule expressed in corneal keratocytes that is responsible for maintaining the avascularity of the cornea.Methods
Human umbilical vein endothelial cells (HUVECs) were cultured with either human dermal fibroblasts or with human corneal keratocytes under serum-free conditions. The areas that exhibited blood vessel formation were estimated by immunostaining the cultures with an antitibody against CD31, a blood vessel marker. We also performed microarray gene-expression analysis and selected one molecule, angiopoietin-like 7 (ANGPTL7) for further functional studies conducted with the keratocytes and in vivo in mice.Results
Areas showing blood vessel formation in normal serum-free medium were conditions were markedly smaller when HUVECs were co-cultured with corneal keratocytes than when they were co-cultured with the dermal fibroblasts under the same conditions. Microarray analysis revealed that ANGPTL7 expression was higher in keratocytes than in dermal fibroblasts. In vitro, inhibiting ANGPTL7 expression by using a specific siRNA led to greater tube formation than did the transfection of cells with a control siRNA, and this increase in tube formation was abolished when recombinant ANGPTL7 protein was added to the cultures. In vivo, intrastromal injections of an ANGPTL7 PshRNA into the avascular corneal stroma of mice resulted in the growth of blood vessels.Conclusions
ANGPTL7, which is abundantly expressed in keratocytes, plays a major role in maintaining corneal avascularity and transparency. 相似文献959.
Takahiko Mitsui Atsuko Araki Ayako Imai Sakiko Sato Chihiro Miyashita Sachiko Ito Seiko Sasaki Takeya Kitta Kimihiko Moriya Kazutoshi Cho Keita Morioka Reiko Kishi Katsuya Nonomura 《PloS one》2015,10(3)
Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D) in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls); testosterone (T), estradiol (E), progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3). A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls) using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01). In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01). No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function. 相似文献
960.
Akira Yokoyama Tetsuji Yokoyama Toshifumi Matsui Takeshi Mizukami Mitsuru Kimura Sachio Matsushita Susumu Higuchi Katsuya Maruyama 《PloS one》2015,10(8)