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31.
Shuxian Jiang Radoslaw Zagozdzon Meritxell Alberich Jorda Kalindi Parmar Yigong Fu John S. Williams Jodi Anne T. Wood Alexandros Makriyannis Naheed Banu Shalom Avraham Jerome E. Groopman Hava Karsenty Avraham 《The Journal of biological chemistry》2010,285(46):35471-35478
Endocannabinoids are lipid signaling molecules that act via G-coupled receptors, CB1 and CB2. The endocannabinoid system is capable of activation of distinct signaling pathways on demand in response to pathogenic events or stimuli, hereby enhancing cell survival and promoting tissue repair. However, the role of endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are maintained in the quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signaling. We report that HSPCs express the CB1 receptors and that BM stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/107 cells), and 2-AG (75.2 ng/107 cells). In response to the endotoxin lipopolysaccharide (LPS), elevated levels of AEA (75.6 pg/107 cells) and 2-AG (98.8 ng/107 cells) were secreted from BM stromal cells, resulting in migration and trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore, administration of exogenous cannabinoid CB1 agonists in vivo induced chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid receptor knock-out mice Cnr1−/− showed a decrease in side population (SP) cells, whereas fatty acid amide hydrolase (FAAH)−/− mice, which have elevated levels of AEA, yielded increased colony formation as compared with WT mice. In addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids and was inhibited by specific cannabinoid antagonists as well as impaired in cannabinoid receptor knock-out mice Cnr1−/−, as compared with WT mice. Thus, we propose a novel function of the endocannabinoid system, as a regulator of HSPC interactions with their BM niches, where endocannabinoids are expressed in HSC niches and under stress conditions, endocannabinoid expression levels are enhanced to induce HSPC migration for proper hematopoiesis. 相似文献
32.
Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats. 总被引:4,自引:0,他引:4
J Prince Vijeya Singh K Selvendiran S Mumtaz Banu R Padmavathi D Sakthisekaran 《Phytomedicine》2004,11(4):309-314
Apigenin, a dietary plant derived flavone subclass of flavonoid is expected to play a role in cancer chemoprevention and cancer chemotherapy. Here we designed our experiment to establish whether treatment of apigenin (25 mg/kg body weight) for 14 consecutive days to (N-nitrosodiethylamine) DEN induced (200 mg/kg body weight; by single ip. injection) and phenobarbital promoted (0.05% through drinking water for 14 successive weeks) rats provide protection against the oxidative stress caused by the carcinogen. The level of lipid peroxidation (LPO) markedly increased in carcinogen administered animals, which was brought back to near normal by apigenin treatment. In contrast the activities/levels of the antioxidant status both in liver and kidney were decreased in carcinogen administered animals, which was recouped back to near normal upon apigenin administration. From our findings we concluded that apigenin prevents LPO and protects antioxidant system in DEN induced and phenobarbital promoted hepatocellular carcinogenesis. 相似文献
33.
Banu Y Matsuda M Yoshihara M Kondo M Sutou S Matsukuma S 《Molecular reproduction and development》2002,61(3):288-301
In a transgenic mouse, Golga3/Mea2 gene (human homolog: GOLGA3/golgin-160) was disrupted by a translocation at the site of the transgene integration. Exons 8-24 of the disrupted gene remained intact and formed a fusion gene (DeltaMea2) with the antisense strand of E. coli-derived transgene by means of a cryptic splice signal in there. The protein product of DeltaMea2, virtually a form truncated to 2/3 of the normal size, localized to Golgi apparatus of pachytene spermatocytes and round spermatids. DeltaMea2 expression was specific to the testis, but varied among separate seminiferous tubules. It also showed variation among homozygous individuals from 0.5 to 4.3% of the wild type (wt) level. At the lowest levels, neither spermatids nor spermatozoa were present in the homozygous testes, but when the expression of DeltaMea2 increased to 4.3% of the wt level, high sperm production was restored and a sporadic (1/22) fertile homozygous male was obtained. The earliest apoptotic degeneration of pachytene spermatocytes evidenced at 17 dpp in homozygous testes in some discrete seminiferous tubules was preceded by DeltaMea2 expression in a variegated fashion at 16 dpp. These results consistently indicated that in homozygous testes, the pachytene spermatocytes which failed to express DeltaMea2 may undergo apoptotic degeneration. Golga3/Mea2, and DeltaMea2 in homozygotes, in a certain excessive amount may be important for survival of pachytene spermatocytes in the mouse. 相似文献
34.
Bukan N Sözen S Coskun U Sancak B Günel N Bozkirli I Senocak C 《European cytokine network》2003,14(3):163-167
BACKGROUND: Both interleukin-18 and nitric oxide are multifunctional molecules that are involved in the different steps of carcinogenesis. METHODS: In the present study, we measured serum interleukin-18 and nitric oxide activity in 51 bladder cancer patients with different tumor stage and grade, and in 8 healthy controls. Serum nitrite-nitrate levels were measured as an index of nitric oxide generation. RESULTS: Serum interleukin-18 levels were significantly higher in bladder cancer patients when compared to the control subjects (p > 0.05). Serum interleukin-18 levels were found to be higher in patients with Ta stage than patients with T1 and T2, T3, T4 stages and in patients with grade 1 tumors than patients with grade 2 and grade 3 tumors, but this was not statistically significant (p > 0.05). There was no significant difference in serum nitrite + nitrate levels between bladder cancer patients and control subjects. CONCLUSIONS: Elevated serum interleukin-18 levels in bladder carcinoma patients may be a result of host defence mechanism against the growth and progression of bladder cancer cells. 相似文献
35.
The toxic effect of vincristine on the apical cells of the rat caput epididymis was investigated. The drug was administered at 20 and 40 microg/kg body weight daily for 15 days. Light microscopy using semithin sections, and transmission electron microscopy, of the caput epididymis were undertaken. The results revealed that the basal region of the apical cell was in contact with the basement membrane and the luminal end took part in endocytosis. The apical cells reflected a dose-dependent response to vincristine (VCR) treatment. In general the changes included protrusion of the apical ends deep into the lumen, with the nucleus of the cell located in such protruded ends, and an increase in the abundance of lysosomal bodies and multivesicular bodies. These changes reflected the physiological response of the apical cell to VCR treatment rather than toxic manifestations. 相似文献
36.
Exonuclease 1 (Exo 1) is an important nuclease involved in mismatch repair system that contributes to maintain genomic stability,
to modulate DNA recombination, and to mediate cell cycle arrest. A guanine (G)/adenine (A) common single nucleotide polymorphism
at first position of codon 589 in Exo 1 gene determines a glutamic acid (Glu, E) to lysine (Lys, K) (K589E) aminoacidic substitution
which may alter cancer risk by influencing the activity of Exo 1 protein. Exo 1 K589E polymorphism has been studied in various
cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. To determine the association
of the Exo 1 K589E polymorphism with the risk of HCC development in a Turkish population, a hospital-based case–control study
was designed consisting of 224 subjects with HCC and 224 cancer-free control subjects matched for age, gender, smoking and
alcohol status. The genotype frequency of the Exo 1 K589E polymorphism was determined by using a polymerase chain reaction–restriction
fragment length polymorphism assay. Our data shows that the Lys/Lys genotype of the Exo 1 K589E polymorphism is associated
with increased risk of HCC development in this Turkish population [odds ratio (OR) = 2.15, 95% confidence interval (CI): 1.13–4.09,
P = 0.02]. Furthermore, according to stratified analysis, a significant association was observed between the homozygote Lys/Lys
genotype and HCC risk in the subgroups of male gender (OR = 2.67, 95% CI: 1.27–5.61, P = 0.009) and patients with non-viral-related HCC (OR = 3.14, 95% CI: 1.09–8.99, P = 0.03). Because our results suggest for the first time that the Lys/Lys homozygote genotype of Exo 1 K589E polymorphism
may be a genetic susceptibility factor for HCC in the Turkish population, further independent studies are required to validate
our findings in a larger series, as well as in patients of different ethnic origins. 相似文献
37.
Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats
Bukan N Sancak B Yavuz O Koca C Tutkun F Ozçelikay AT Altan N 《Indian journal of biochemistry & biophysics》2003,40(6):447-450
In this study, alterations in the liver antioxidant enzymes status and lipid peroxidation in short-term (8-weeks) and long-term (24-weeks) diabetic rats were examined. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly increased, but superoxide dismutase (SOD) activity was significantly reduced in 8-weeks diabetic rats, compared to control. Catalase (CAT) activity, however, was found unchanged. In 24-weeks diabetic rats, while GSH-Px activity was unchanged, but SOD and CAT activities and MDA levels were significantly increased, compared to control. These results suggest that diabetes-induced alterations in tissue antioxidant system may reflect a generalized increase in tissue oxidative stress. It can be concluded that lipid peroxidation and antioxidant enzyme levels are elevated in diabetic condition. Hence, diabetes mellitus, if left untreated, may increase degenerative processes due to accumulation of oxidative free radicals. 相似文献
38.
Ashini Bolia Brian W. Woodrum Angelo Cereda Melissa A. Ruben Xu Wang S. Banu Ozkan Giovanna Ghirlanda 《Biophysical journal》2014
Cyanovirin-N (CVN), a cyanobacterial lectin, exemplifies a class of antiviral agents that inhibit HIV by binding to the highly glycosylated envelope protein gp120. Here, we investigate the energetics of glycan recognition using a computationally inexpensive flexible docking approach, backbone perturbation docking (BP-Dock). We benchmarked our method using two mutants of CVN: P51G-m4-CVN, which binds dimannose with high affinity through domain B, and CVN(mutDB), in which binding to domain B has been abolished through mutation of five polar residues to small nonpolar side chains. We investigated the energetic contribution of these polar residues along with the additional position 53 by docking dimannose to single-point CVN mutant models. Analysis of the docking simulations indicated that the E41A/G and T57A mutations led to a significant decrease in binding energy scores due to rearrangements of the hydrogen-bond network that reverberated throughout the binding cavity. N42A decreased the binding score to a level comparable to that of CVN(mutDB) by affecting the integrity of the local protein structure. In contrast, N53S resulted in a high binding energy score, similar to P51G-m4-CVN. Experimental characterization of the five mutants by NMR spectroscopy confirmed the binding affinity pattern predicted by BP-Dock. Despite their mostly conserved fold and stability, E41A, E41G, and T57A displayed dissociation constants in the millimolar range. N53S showed a binding constant in the low micromolar range, similar to that observed for P51G-m4-CVN. No binding was observed for N42A. Our results show that BP-Dock is a useful tool for rapidly screening the relative binding affinity pattern of in silico-designed mutants compared with wild-type, supporting its use to design novel mutants with enhanced binding properties. 相似文献
39.
Emel Banu Buyukunal Bal Suleyman Bayar Mehmet Ali Bal 《Journal of microbiology (Seoul, Korea)》2010,48(3):267-274
The prevalence and antimicrobial susceptibilities of Staphylococci and Streptococci were assessed from subclinical mastitis
cases. One hundred Coagulase-Negative Staphylococci (CNS) and 34 Streptoccocci were identified. The most frequently isolated
species were Staphylococcus haemolyticus (27%) and Staphylococcus simulans (24%). Susceptible CNS species revealed the highest resistance to penicillin G (58%), ampicillin (48%), neomycin (20%), and
oleandomycin (14%). CNS methicillin resistance rates within 82 isolates were 21.95% and 1.22% by disk diffusion and PCR methods,
respectively. These results suggested the disk diffusion method was more prone to yield false positives. Partial sequencing
of the 16S rRNA region from the mecA carrying isolate (S. haemolyticus) was homologous with S. haemolyticus sequences/accessions obtained from GenBank. However, the mecA gene sequence from this isolate was more closely allied with the S. aureus mecA gene of human origins. Identical sequence data was acquired from the National Center for Biotechnology Information (NCBI)
database, suggesting horizontal gene transfer between the two species. CNS β-lactamase activity within 81 isolates was 29.63%.
The most frequently isolated Streptococcus species were S. uberis (52%) and S. agalactiae (15%). Oleandomycin was the least effective antimicrobial agent on these isolates with 59% susceptibility. Results indicated
that CNS and Streptococci exhibited various antimicrobial resistance responses. Consequently, isolation and identification
of udder pathogens in herds suffering from subclinical agents is essential to select the most effective antimicrobial agent.
Moreover, multiple resistance features of methicillin resistant (MR) isolates should be considered during antimicrobial susceptibility
tests. 相似文献
40.
William Ba-Thein Satoko Inui Tohru Shimizu Tint Swe Sayera Banu Kaori Ohtani Misari Oe Naomi Sakurai Shinichi Nakamura Hideo Hayashi 《Microbiology and immunology》1997,41(8):629-631
The genomic structure of the pfoA-colA region in six theta-toxin-deficient strains of Clostridium perfringens was examined by Southern hybridization using the pfoR, pfoA, pbg, arcABDC and colA genes, encoding regulator for pfoA, theta-toxin, beta-galactosidase, arginine metabolism enzymes and kappa-toxin, respectively, as gene probes. It is suggested that the productivity of theta-toxin in these strains is diverse because of the multiple genetic backgrounds including single deletion of pfoA, large deletion of the pfoA-colA region and the putative point mutations. 相似文献