首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   6941篇
  免费   498篇
  国内免费   467篇
  2024年   8篇
  2023年   60篇
  2022年   184篇
  2021年   332篇
  2020年   200篇
  2019年   280篇
  2018年   255篇
  2017年   211篇
  2016年   276篇
  2015年   443篇
  2014年   500篇
  2013年   517篇
  2012年   620篇
  2011年   565篇
  2010年   385篇
  2009年   321篇
  2008年   377篇
  2007年   329篇
  2006年   294篇
  2005年   263篇
  2004年   224篇
  2003年   175篇
  2002年   167篇
  2001年   118篇
  2000年   97篇
  1999年   102篇
  1998年   50篇
  1997年   62篇
  1996年   64篇
  1995年   53篇
  1994年   38篇
  1993年   43篇
  1992年   52篇
  1991年   47篇
  1990年   36篇
  1989年   27篇
  1988年   16篇
  1987年   28篇
  1986年   21篇
  1985年   17篇
  1984年   5篇
  1983年   7篇
  1982年   6篇
  1981年   5篇
  1980年   4篇
  1973年   3篇
  1971年   3篇
  1968年   2篇
  1967年   2篇
  1962年   2篇
排序方式: 共有7906条查询结果,搜索用时 357 毫秒
231.

Aim

Understanding and predicting ecosystem functioning such as biomass accumulation requires an accurate assessment of large-scale patterns of biomass distribution and partitioning in relation to climatic and soil environments.

Methods

We sampled above- and belowground biomass from 26 sites spanning 1500 km in Inner Mongolian grasslands, compared the difference in aboveground, belowground biomass and below-aboveground biomass ratio (AGB, BGB, and B/A, respectively) among meadow steppe, typical steppe, and desert steppe types. The relationships between AGB, BGB, B/A and climatic and soil environments were then examined.

Results

We found that AGB and BGB differed significantly among three types of grasslands while B/A did not differ. Structural equation model analyses indicated that mean annual precipitation was the strongest positive driver for AGB and BGB. AGB was also positively associated with soil organic carbon, whereas B/A was positively associated with total soil nitrogen.

Conclusions

These results indicated that precipitation positively influence plant production in Inner Mongolian grasslands. Contrary to the prediction from the optimal partitioning hypothesis, biomass allocation to belowground increased with soil total nitrogen, suggesting that more productive sites may increase belowground allocation as an adaptive strategy to potentially high fire frequencies.  相似文献   
232.
A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G > T and rs2274224 C > G) of PLCE1 in a population-based case–control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45–5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46–0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (Ptrend = 0.005). The Grs17417407Ars2274223Crs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62–0.93), meanwhile the Grs17417407Grs2274223Crs2274224 and Trs17417407Grs2274223Crs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33–2.18 and OR, 2.51; 95% CI, 1.15–2.49). Gene–environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the “high risk group” with 3.67-fold (OR: 3.67, 95% CI: 2.74–4.92), compared to the “low risk group”. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.  相似文献   
233.
We determined the complete mitochondrial DNA (mtDNA) sequence of a fluke, Paramphistomum cervi (Digenea: Paramphistomidae). This genome (14,014 bp) is slightly larger than that of Clonorchis sinensis (13,875 bp), but smaller than those of other digenean species. The mt genome of P. cervi contains 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 non-coding regions (NCRs), a complement consistent with those of other digeneans. The arrangement of protein-coding and ribosomal RNA genes in the P. cervi mitochondrial genome is identical to that of other digeneans except for a group of Schistosoma species that exhibit a derived arrangement. The positions of some transfer RNA genes differ. Bayesian phylogenetic analyses, based on concatenated nucleotide sequences and amino-acid sequences of the 12 protein-coding genes, placed P. cervi within the Order Plagiorchiida, but relationships depicted within that order were not quite as expected from previous studies. The complete mtDNA sequence of P. cervi provides important genetic markers for diagnostics, ecological and evolutionary studies of digeneans.  相似文献   
234.
A density functional theory (DFT) study was performed to explore the mechanisms of the acid-catalyzed decarboxylation reaction of salicylic acids using the B3LYP method with 6-31++G(d,p) basis set in both gas phase and aqueous environment. The α-protonated cation of carboxylate acid was formed during the decarboxylation process in acidic conditions, and the presence of hydrogen ions promotes decarboxylation greatly by significantly decreasing the overall reaction energy barriers to 20.98 kcal mol?1 in gas phase and 20.93 kcal mol?1 in water, respectively. The hydrogen in the α-carbon came directly from the acid rather than from the carboxyl group in neutral state. Compared with the reaction in gas phase, water in aqueous state causes the reaction to occur more easily. Substituents of methyl group, chlorine and fluorine at the ortho-position to the carboxyl of salicylic acid could further lower the decarboxylation energy barriers and facilitate the reaction.  相似文献   
235.
A wearable scanning photoacoustic imaging (wPAI) system is presented for noninvasive brain study in behaving rats. This miniaturized wPAI system consists of four pico linear servos and a single transducer‐based PAI probe. It has a dimension of 50 mm × 35 mm × 40 mm, and a weight of 26 g excluding cablings. Phantom evaluation shows that wPAI achieves a lateral resolution of ~0.5 mm and an axial resolution of ~0.1 mm at a depth of up to 11 mm. Its imaging ability is also tested in a behaving rat, and the results indicate that wPAI is able to image blood vessels at a depth of up to 5 mm with intact scalp and skull. With its noninvasive, deep penetration, and functional imaging ability in behaving animals, wPAI can be used for behavior, cognition, and preclinical brain disease studies.

  相似文献   

236.

Purpose

Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography.

Methods

Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch’s membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.

Results

The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > –6 dB) and moderate-to-advanced glaucoma (MD < –6 dB, P = 0.95).

Conclusions

LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change.  相似文献   
237.
Electron transfer between cytochrome c (Cytc) and electrodes can be influenced greatly by the orientation of protein on the surface of the electrodes. In the present study, different initial orientations of Cytc on the surface of five types of single-walled carbon nanotubes (SWNTs), with different diameters and chirality, were constructed. Properties of the orientations of proteins on the surface of these tubes were first investigated through molecular dynamics simulations. It was shown that variations in SWNT diameter do not significantly affect the orientation; however, the chirality of the SWNTs is crucial to the orientation of the heme embedded in Cytc, and the orientation of the protein can consequently be influenced by the heme orientation. A new electron pathway between Cytc and SWNT, which hopefully benefits electron transfer efficiency, has also been proposed. This study promises to provide theoretical guidance for the rational design of bio-sensors or bio-fuel cells by using Cytc-decorated carbon nanotube electrodes.  相似文献   
238.
239.
Large‐scale bioprocessing is key to the successful manufacturing of a biopharmaceutical. However, cell viability and productivity are often lower in the scale‐up from laboratory to production. In this study, we analyzed CHO cells, which showed lower percent viabilities and productivity in a 5‐KL production scale bioreactor compared to a 20‐L bench‐top scale under seemingly identical process parameters. An increase in copper concentration in the media from 0.02 µM to 0.4 µM led to a doubling of percent viability in the production scale albeit still at a lower level than the bench‐top scale. Combined metabolomics and proteomics revealed the increased copper reduced the presence of reactive oxygen species (ROS) in the 5‐KL scale process. The reduction in oxidative stress was supported by the increased level of glutathione peroxidase in the lower copper level condition. The excess ROS was shown to be due to hypoxia (intermittent), as evidenced by the reduction in fibronectin with increased copper. The 20‐L scale showed much less hypoxia and thus less excess ROS generation, resulting in little to no impact to productivity with the increased copper in the media. The study illustrates the power of 'Omics in aiding in the understanding of biological processes in biopharmaceutical production.  相似文献   
240.
C Dou  N Ding  J Xing  C Zhao  F Kang  T Hou  H Quan  Y Chen  Q Dai  F Luo  J Xu  S Dong 《Cell death & disease》2016,7(3):e2162
Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant Artemisia annua. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In vivo study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss.Bone is a dynamic organ that undergoes continuous remodeling throughout life. Bone homeostasis is maintained by a balanced bone-resorbing and bone-forming process. In this process, hematopoietic stem cells or monocytes/macrophage progenitor cell-derived osteoclasts (OCs) are mainly responsible for bone resorption.1 Abnormal OC function is associated with numerous diseases, and most of them are due to excessive osteoclastic activity. These diseases include osteoporosis, rheumatoid arthritis and periodontitis.2, 3 Two of the most important regulating factors during OC differentiation are receptor activator of nuclear factor κB ligand (RANKL) and macrophage-colony-stimulating factor (M-CSF).4, 5 Binding of RANKL to RANK results in the initiation of the TNF receptor-associated factor 6 signaling, which activates nuclear factor-κB, Akt and MAP kinase (ERk, JNK and p-38), and eventually leads to the proliferation, differentiation and maturation of OCs.6, 7Lipopolysaccharide (LPS) is an important component of the outer membrane of Gram-negative bacteria. In LPS-induced bone loss, many factors are involved including local host response, prostanoids and cytokine production, inflammatory cell recruitment and OC activation.8, 9, 10 Experimental evidence have shown that LPS-mediated inflammation is highly dependent on reactive oxygen species (ROS) and the associated downstream MAPK signaling pathways including ERK, JNK and p-38.11, 12 ROS has been shown having an important role in the process of OC differentiation, survival, activation and bone resorption.13, 14, 15, 16 It has also been proved that ROS production in OC and intracellular hydrogen peroxide accumulation is critical for osteoclastogenesis and skeletal homeostasis.17 Recently, a study reported that LPS induces OC formation via the ROS-mediated JNK and STAT3 pathway, which could be blocked by peroxiredoxin II.18Dihydroartemisinin (DHA) is the main active metabolite isolated from the plant Artemisia annua. DHA has been widely used as first-line therapeutics against falciparum malaria.19 Recent evidence suggested that DHA has antitumor effects because of its unique cytotoxicity mechanism.20 In particular, studies reported that DHA is pro-apoptotic in tumor cell lines regarding breast and prostate cancer.21, 22 Although the detailed mechanism of DHA cytotoxicity and pro-apoptotic effects is not fully understood, DHA-mediated ROS production has a central role.23, 24 However, the effect of DHA on bone health has not been studied.In the present study, we reported that DHA could attenuate LPS-induced OC differentiation, fusion and bone-resorption activity in vitro. Our data showed that DHA-induced cell apoptosis during LPS-induced osteoclastogenesis via intracellular ROS generation and mitochondria-mediated pathways. DHA administration in LPS-induced mouse models decreased OC number and reversed bone loss in vivo.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号