全文获取类型
收费全文 | 26087篇 |
免费 | 2144篇 |
国内免费 | 2034篇 |
专业分类
30265篇 |
出版年
2024年 | 76篇 |
2023年 | 325篇 |
2022年 | 845篇 |
2021年 | 1238篇 |
2020年 | 852篇 |
2019年 | 1052篇 |
2018年 | 1082篇 |
2017年 | 766篇 |
2016年 | 1098篇 |
2015年 | 1564篇 |
2014年 | 1808篇 |
2013年 | 2004篇 |
2012年 | 2393篇 |
2011年 | 2117篇 |
2010年 | 1356篇 |
2009年 | 1225篇 |
2008年 | 1474篇 |
2007年 | 1311篇 |
2006年 | 1132篇 |
2005年 | 1043篇 |
2004年 | 854篇 |
2003年 | 797篇 |
2002年 | 687篇 |
2001年 | 497篇 |
2000年 | 403篇 |
1999年 | 387篇 |
1998年 | 287篇 |
1997年 | 197篇 |
1996年 | 141篇 |
1995年 | 149篇 |
1994年 | 111篇 |
1993年 | 91篇 |
1992年 | 124篇 |
1991年 | 117篇 |
1990年 | 104篇 |
1989年 | 73篇 |
1988年 | 62篇 |
1987年 | 56篇 |
1986年 | 43篇 |
1985年 | 53篇 |
1984年 | 28篇 |
1983年 | 28篇 |
1982年 | 24篇 |
1981年 | 14篇 |
1979年 | 20篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1976年 | 15篇 |
1975年 | 14篇 |
1972年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Kwon EM Holt SK Fu R Kolb S Williams G Stanford JL Ostrander EA 《Cancer epidemiology》2012,36(4):347-353
Background: Prostate cancer (PC) is the most frequently diagnosed solid tumor in U.S. men. Genome-wide association studies (GWAS) have identified over 40 risk-associated single nucleotide polymorphisms (SNPs), including variants in androgen pathway genes (e.g., KLK3 and AR). Androgens are important in PC and genes involved in this pathway are therefore candidates for conferring susceptibility to PC. Methods: In this hypothesis-testing study, we evaluated PC risk in association with SNPs in 22 candidate genes involved in androgen metabolism or interactions with the androgen receptor (AR). A total of 187 SNPs were genotyped in 1458 cases and 1351 age-matched controls from a population-based study. PC risk was estimated using adjusted unconditional logistic regression and multinomial regression models. Results: Single SNP analyses showed evidence (p < 0.05) for associations with 14 SNPs in 9 genes: NKX3.1, HSD17B3, AKR1C3, SULT2A1, CYP17A1, KLK3, JAK2, NCOA4 and STAT3. The most significant result was observed for rs2253502 in HSD17B3 (odds ratio, OR = 0.57, 95% CI: 0.39–0.84). In addition, five SNPs in four genes (CYP17A1, HSD17B4, NCOA4, and SULT2A1) were associated with more aggressive disease (p < 0.01). Conclusions: Our results replicate previously reported associations for SNPs in CYP17A1, HSD17B3, ARK1C3, NKX3.1, NCOA4 and KLK3. In addition, novel associations were observed for SNPs in JAK2, HSD17B4, and SULT2A1. These results will require replication in larger studies. 相似文献
962.
BackgroundThe accumulation of advanced glycated end products (AGEs) in retinal blood vessels is one of the major etiological factors contributing to diabetic retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors of AGEs formation. The aim of this study was to investigate whether AG could protect the development of diabetic retinopathy through inhibition of AGEs.MethodsRat diabetes was induced by intraperitoneal injection with streptozotocin (STZ). AG was given to rats in drinking water. Retina was extracted 3 and 6 months following STZ and AG administration. Immunochemistry and transmission electron microscope were used to detect the expression of AGEs and retina morphology.ResultsExtensive staining of AGEs was detected in retinal blood vessels of 3- and 6-month diabetic rats, while no significant staining was found in the control non-diabetic retina or AG treated groups. Pericyte loss, endothelial cell proliferation, increased ratio of endothelial cells/pericytes, acellular capillaries and capillary occlusion were observed in the retina of 6-month diabetic rats. The increased electron density of retinal capillary basement membrane, mitochondrial swelling in pericytes and endothelial cells were also found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats did not have similar morphological changes compared to control group. The AGEs staining in AG-treated rats was still weakly positive.ConclusionsAGEs plays pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal microvasculature changes. AG could prevent the onset and development of diabetic retinopathy through inhibition of AGEs. 相似文献
963.
Here, we report a novel porcine circovirus type 2a (PCV2a) strain with 11 nucleotides (nt) inserted in the origin of genome replication (Ori). This is the first report of a PCV2a strain with nucleotide insertion in Ori. Our study will help further epidemiological studies and extend our knowledge of evolutionary characteristics of PCV2. 相似文献
964.
Li JS Han Q Fang J Rizzi M James AA Li J 《Archives of insect biochemistry and physiology》2007,64(2):74-87
Tryptophan 2,3-dioxygenase (TDO) is the first enzyme in the tryptophan oxidation pathway. It is a hemoprotein and its heme prosthetic group is present as a heme-ferric (heme-Fe(3+)) form that is not active. To be able to oxidize tryptophan, the heme-Fe(3+) form of the enzyme must be reduced to a heme-ferrous (heme-Fe(2+)) form and this study describes conditions that promote TDO activation. TDO is progressively activated upon mixing with tryptophan in a neutral buffer, which leads to an impression that tryptophan is responsible for TDO activation. Through extensive analysis of factors resulting in TDO activation during incubation with tryptophan, we conclude that tryptophan indirectly activates TDO through promoting the production of reactive oxygen species. This consideration is supported by the virtual elimination of the initial lag phase when either pre-incubated tryptophan solution was used as the substrate or a low concentration of superoxide or hydrogen peroxide was incorporated into the freshly tryptophan and TDO mixture. However, accumulation of these reactive oxygen species also leads to the inactivation of TDO, so that both TDO activation and inactivation proceed with the specific outcome depending greatly on the concentrations of superoxide and hydrogen peroxide. As a consequence, the rate of TDO catalysis varies depending upon the proportion of the active to inactive forms of the enzyme, which is in a dynamic relationship in the reaction mixture. These data provide some insight towards elucidating the molecular regulation of TDO in vivo. 相似文献
965.
Kang BJ Jung JH Lee JM Lim SG Saito H Kim MH Kim YJ Saigusa M Han CH 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,148(4):445-453
We cloned and sequenced two vitellogenin (vg) cDNAs of the carp, Cyprinus carpio, using a cDNA library constructed from estradiol-17β (E2)-treated livers. One was a novel, longer 5000 bp-long cDNA termed vg-B2 encoding 1624 amino acids in a single open reading frame. The other was a shorter cDNA (vg-B1), identical to that registered previously as carp vg cDNA in the international nucleotide sequence database. The deduced amino acid sequences of these two molecules were well-aligned with known vertebrate Vgs sharing common characteristics such as N-terminal lipovitellin I (LVI), phosvitin (PV) and C-terminal lipovitellin II (LVII). The novel Vg-B2 bore a highly conserved GL/ICG motif within the LVII region, in contrast to the shorter Vg-B1 that has a truncated C-terminal and lacks the β-component within the LVII region including the GL/ICG motif. Both vg-B2 and vg-B1 genes were expressed in the livers of females and E2-injected males. Western blot analysis using anti-Vg and anti-vitellin (Vn) antisera demonstrated that both Vg-B2 and Vg-B1 were detected as polypeptides with an estimated molecular mass of 180 kDa and 160 kDa, respectively, in the blood of females and E2-injected males. The results suggest the potential utilization of these genes as sensitive xenoestrogenic markers. 相似文献
966.
S100在猫小脑中的分布及其表达的年龄相关性变化 总被引:1,自引:1,他引:1
用免疫组织化学ABC法标记S100免疫阳性(S100-IR)细胞,观察S100蛋白在青年猫和老年猫小脑中的分布,探讨其表达的年龄相关变化及意义。光镜下计数颗粒层和髓质中S100-IR细胞密度及浦肯野细胞(PC)层阳性细胞线密度。结果显示,颗粒层和髓质中S100-IR细胞密度较小、分布均匀,PC层阳性细胞相对密集,分子层未见阳性反应;阳性细胞胞浆深染。与青年猫相比,老年猫小脑颗粒层、髓质和PC层中S100-IR细胞密度显著增加(P<0.01),胞体较大,阳性较强。表明S100-IR细胞在小脑中的分布具区域性差异,呈明显的年龄相关性增生,推测其增生对衰老神经元的丢失起保护作用。 相似文献
967.
Immuno-stimulating effect of the endo-polysaccharide produced by submerged culture of Inonotus obliquus 总被引:12,自引:0,他引:12
Inonotus obliquus BELYU1102 was selected from 12 different strains of Inonotus as a producer of immuno-stimulating polysaccharide. After a batch fermentation of I. obliquus BELYU1102 was carried out in a 300 l pilot vessel, endo-polysaccharide and exo-polysaccharide were both obtained. The proliferation activity of endo-polysaccharide for splenic cells was much higher than the activity of exo-polysaccharide. The active endo-polysaccharide was produced primarily during the late stationary phase. Enhanced proliferation and polyclonal IgM antibody production were observed in B cells by purified water-soluble endo-polysaccharide. Nitrite production and expression of IL-1beta, IL-6, TNF-alpha, and iNOS in macrophages were also enhanced. However, the endo-polysaccharide did not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the IL-4 expression of Th2 cells. The endo-polysaccharide showed activities similar to lipopolysaccharide (LPS) for B cells and macrophages, but there was a large difference between the two polysaccharides because cellular activations induced by endo-polysaccharide were not affected by polymyxin B, a specific inhibitor of LPS. The endo-polysaccharide appeared to have other cellular binding sites with TLR-4 and did not show a direct toxicity against tumor cells. However, indirect anti-cancer effects via immuno-stimulation were observed. The mycelial endo-polysaccharide of I. obliquus is a candidate for use as an immune response modifier. Submerged mycelial cultures are advantageous for industrial production of polysaccharides. 相似文献
968.
A novel lectin (AMML) was isolated from a Chinese herb, i.e., the roots of Astragalus mongholicus, using a combination of ammonium sulfate fraction and ion exchange chromatographies. The molecular mass of intact AMML was determined to be 66,396 Da by MALDI-TOF mass spectrometry and 61.8 kDa by gel filtration, respectively. AMML was a dimeric protein composed of two identical subunits each with a molecular mass of 29.6 kDa. The lectin was a glycoprotein with a neutral carbohydrate content of 19.6%. The purified lectin hemagglutinated both rabbit and human erythrocytes, and showed preference for blood types O (native) and AB (trypsin-treated). Among various carbohydrates tested, the lectin was best inhibited by D-galactose and its derivatives with pronounced preference for lactose (3.13 mM). N-terminal amino acid sequence of AMML was determined as ESGINLQGDATLANN. The optimal pH range for lectin activity was between pH 4.5 and 7.5, and the lectin was active up to 65 degrees C. It also exerted antifungal activity against Botrytis cincerea, Fusarium oxysporum, Colletorichum sp., and Drechslera turcia but not against Rhizoctonia solani and Mycosphaerella arachidicola. 相似文献
969.
The study focused on the dynamics of Malondialdehyde (MDA) contents and the activities of protective enzymes in the leaves of alfalfa varieties with various resistances to Aphis medicaginis Koch. The results showed that susceptible varieties always had higher MDA contents than resistant varieties, and the MDA contents tended to rise in both susceptible and resistant varieties in period of the varieties were pierced and sucked by aphids. Superoxide dismutase (SOD), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities in susceptible varieties were lower than those in resistant varieties, and in both susceptible and resistant varieties the SOD and POD activities tended to rise at first and then decline, and the PAL activities rose to their peaks and then tended to remain stable. In the susceptible and resistant varieties the catalase (CAT) activities appeared to rise and decline alternatively; the PPO activities in resistant varieties were lower than those in susceptible varieties in early growth, but higher than those in susceptible varieties in later growth. It follows that infested by aphids, susceptible and resistant varieties had the MDA contents, variations of SOD, POD, PAL and PPO activities were closely correlated with their aphid resistances, hence these indexes could be used as physiological indexes for testing aphid resistance of alfalfa, whereas the relations of their CAT activities to their resistances needed to be further studied. 相似文献
970.