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911.
The aim of this study was to evaluate the drug susceptibility of P. aeruginosa strains and to detect strains producing inducible beta-lactamases (IBL), extended-spectrum beta-lactamases (ESBL), and metallo-beta-lactamases (MBL). During 6 month (October 2005 - March 2006), 66 strains of P. aeruginosa strains were cultured from clinical specimens obtained from patients of two of hospitals in Siedlce and from patients of outpatient clinics. All the strains were identified in the automatic ATB (bio Mérieux). The susceptibility of bacteria to antibiotics was tested by standard disc diffusion method. The majority of strains were susceptible to meropenem (89.4%), piperacillin combined with tazobactam (84.8%), ciprofloxacin (84.8%) and piperacillin (83.3%). Many of our strains were resistant to carbenicillin (69.7%), mezlocillin (45.5%), gentamicin (42.4%) and netylmicin (30.3%). 6 strains (9.1%) were multidrug-resistant (MDR). Inducible beta-lactamases were detected with the use double disc method according to Sanders and Sanders. ESBL-producing strains were detected with double disc test (DDST) according to Jarlier et al. These strains were identified as ESBL-positive on the basis of the DDST were also determined using a double disc (DD) test according to Appleton. Production of metallo-beta-lactamases (MBL) was examined with the use of Etest MBL (AB Biodisk, Sweden) and the double disc test according to Arakava et al. Sixty-five IBL-producing strains (98.5% of all strains) and three strains (4.5%) with MBL activity were detected. Strains producing extended beta-lactamases (ESBL) were not found. 相似文献
912.
M. Staub T. Szpaszokukockaja M. Bencsáth F. Antoni K. Lapis 《Chemico-biological interactions》1982,41(2):181-192
The activity of DNA polymerases and thymidine kinase was compared in the MC-29 leukosis virus-induced transplantable hepatoma and in the livers of rats treated with cyclophosphamide (CP), cytosine-arabinoside (ara-C) and 5-fluoro-uracil (5-FU). The specific activity of DNA polymerase was twenty times greater in the MC-29 leukosis virus-induced hepatoma, while thymidine kinase was only 3–5 times greater than in the liver.All three enzymes showed Michaelis-Menten kinetics in their substrate and template saturation curves. The template utilization of DNA polymerases from hepatoma and from liver was compared. Both had higher activities on a poly(dA) · poly(dT) template at pH 8.0, than on DNA at pH 7.5. After chromatography on a phosphocellulose column two polymerases were separated. The first peak eluted by 0.15 M KCl preferred DNA as template (polymerase α). The second eluted by 0.5 M KCl worked better on poly(dA) · poly(dT) (polymerase β). Thymidine kinase was eluted by 0.25 M KCl. Inhibition by N-ethylmaleimide (NEM) showed the polymerase α to be sensitive and the polymerase β to be resistant to the sulfhydryl blocking agent; similar to the respective enzymes of other eukaryotic cells. The specific acitivity of DNA polymerase decreased after CP treatment at 6 h and 72 h and after ara-C treatment at 72 h. The specific activities of thymidine kinase were not changed significantly in response to the drug administrations. 相似文献
913.
Begley J Vo DD Morris LF Bruhn KW Prins RM Mok S Koya RC Garban HJ Comin-Anduix B Craft N Ribas A 《Cancer immunology, immunotherapy : CII》2009,58(5):699-708
Several tumor immunotherapy approaches result in a low percentage of durable responses in selected cancers. We hypothesized
that the insensitivity of cancer cells to immunotherapy may be related to an anti-apoptotic cancer cell milieu, which could
be pharmacologically reverted through the inhibition of antiapoptotic Bcl-2 family proteins in cancer cells. ABT-737, a small
molecule inhibitor of the antiapoptotic proteins Bcl-2, Bcl-w and Bcl-xL, was tested for the ability to increase antitumor immune responses in two tumor immunotherapy animal models. The addition
of systemic therapy with ABT-737 to the immunization of BALB/c mice with tumor antigen peptide-pulsed dendritic cells (DC)
resulted in a significant delay in CT26 murine colon carcinoma tumor growth and improvement in survival. However, the addition
of ABT-737 to either a vaccine strategy involving priming with TRP-2 melanoma antigen peptide-pulsed DC and boosting with
recombinant Listeria monocytogenes expressing the same melanoma antigen, or the adoptive transfer of TCR transgenic cells, did not result in superior antitumor
activity against B16 murine melanoma. In vitro studies failed to demonstrate increased cytotoxic lytic activity when testing
the combination of ABT-737 with lymphokine activated killer (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand
or TNF-alpha against the CT26 and B16 cell lines. In conclusion, the Bcl-2 inhibitor ABT-737 sensitized cancer cells to the
antitumor effect of antigen-specific immunotherapy in a vaccine model for the CT26 colon carcinoma in vivo but not in two
immunotherapy strategies against B16 melanoma. 相似文献
914.
Agnieszka Kubiak Piotr Jakimowicz Antoni Polanowski 《International journal of biological macromolecules》2009,45(2):194-199
Low-molecular-mass trypsin inhibitor (clTI-1; chicken liver Trypsin Inhibitor-1) was purified from chicken liver by extraction with perchloric acid, ammonium sulfate precipitation, a combination of ethanol-acetone fractionation followed by gel filtration, ion-exchange chromatography and RP-HPLC on a C18 column. The inhibitor occurs in two isoforms with molecular masses of 5938.56 and 6026.29 Da (determined by MALDI TOFF mass spectrometry). The complete amino acid sequences of both isoforms were determined (UniProtKB/Swiss-Prot P85000; ISK1L_CHICK). The inhibitor shows a high homology to Kazal-type family inhibitors, especially to trypsin/acrosin inhibitors and pancreatic secretory trypsin inhibitors. clTI-1 inhibits both bovine and porcine trypsin (Ka = 1.1 × 109 M?1 and 2.5 × 109 M?1, respectively). Significant differences were shown in the inhibition of the anionic and cationic forms of chicken trypsin (Ka = 4.5 × 108 M?1 and 1.2 × 1010 M?1). Weak interaction with human plasmin (Ka = 1.2 × 107 M?1) was also revealed. 相似文献
915.
Bego?a Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C. Koya Antoni Ribas 《PloS one》2010,5(9)
Background
The effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.Methodology/Principal
Findings Intracellular flow cytometry was used to detect phosphorylated (p) signaling molecules downstream of the T cell receptor (TCR) and cytokine receptors. PBMC from tremelimumab-treated patients were characterized by increase in pp38, pSTAT1 and pSTAT3, and decrease in pLck, pERK1/2 and pSTAT5 levels. These changes were noted in CD4 and CD8 T lymphocytes but also in CD14 monocytes. A divergent pattern of phosphorylation of Zap70, LAT, Akt and STAT6 was noted in patients with or without an objective tumor response.Conclusions/Significance
The administration of the CTLA4-blocking antibody tremelimumab to patients with metastatic melanoma influences signaling networks downstream of the TCR and cytokine receptors both in T cells and monocytes. The strong modulation of signaling networks in monocytes suggests that this cell subset may be involved in clinical responses to CTLA4 blockade.Clinical Trial Registration
clinicaltrials.gov; Registration numbers and NCT00090896 NCT00471887相似文献916.
917.
Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin 总被引:10,自引:0,他引:10
Ma K Cabrero A Saha PK Kojima H Li L Chang BH Paul A Chan L 《The Journal of biological chemistry》2002,277(38):34658-34661
Previous reports showed that recombinant fragments of adiponectin (adipo) displayed pharmacological effects when injected into rodents, but the relevance of these observations to the physiological function of adipo is unclear. We generated Adipo(-/-) mice by gene targeting. Adipo(-/-) mice are fertile with normal body and fat pad weights. Plasma glucose and insulin levels of Adipo(-/-) and Adipo(+/+) mice are similar under fasting conditions and during an intraperitoneal glucose tolerance test (GTT). Insulin tolerance test (ITT) also produces similar plasma glucose and insulin levels in the two groups of mice. Hyperinsulinemic-euglycemic clamp analysis showed that Adipo(-/-) and Adipo(+/+) mice have similar glucose infusion rates to maintain a similar serum glucose. High-fat diet feeding for 7 months led to similar weight gain and similar GTT and ITT responses. We next measured beta-oxidation and found it to be significantly increased in muscle and liver of Adipo(-/-) mice. In conclusion, our study indicates that absence of adipo causes increased beta-oxidation but does not cause glucose intolerance or insulin resistance in mice. 相似文献
918.
Pires VM Henshaw JL Prates JA Bolam DN Ferreira LM Fontes CM Henrissat B Planas A Gilbert HJ Czjzek M 《The Journal of biological chemistry》2004,279(20):21560-21568
Glycoside hydrolases that release fixed carbon from the plant cell wall are of considerable biological and industrial importance. These hydrolases contain non-catalytic carbohydrate binding modules (CBMs) that, by bringing the appended catalytic domain into intimate association with its insoluble substrate, greatly potentiate catalysis. Family 6 CBMs (CBM6) are highly unusual because they contain two distinct clefts (cleft A and cleft B) that potentially can function as binding sites. Henshaw et al. (Henshaw, J., Bolam, D. N., Pires, V. M. R., Czjzek, M., Henrissat, B., Ferreira, L. M. A., Fontes, C. M. G. A., and Gilbert, H. J. (2003) J. Biol. Chem. 279, 21552-21559) show that CmCBM6 contains two binding sites that display both similarities and differences in their ligand specificity. Here we report the crystal structure of CmCBM6 in complex with a variety of ligands that reveals the structural basis for the ligand specificity displayed by this protein. In cleft A the two faces of the terminal sugars of beta-linked oligosaccharides stack against Trp-92 and Tyr-33, whereas the rest of the binding cleft is blocked by Glu-20 and Thr-23, residues that are not present in CBM6 proteins that bind to the internal regions of polysaccharides in cleft A. Cleft B is solvent-exposed and, therefore, able to bind ligands because the loop, which occludes this region in other CBM6 proteins, is much shorter and flexible (lacks a conserved proline) in CmCBM6. Subsites 2 and 3 of cleft B accommodate cellobiose (Glc-beta-1,4-Glc), subsite 4 will bind only to a beta-1,3-linked glucose, whereas subsite 1 can interact with either a beta-1,3- or beta-1,4-linked glucose. These different specificities of the subsites explain how cleft B can accommodate beta-1,4-beta-1,3- or beta-1,3-beta-1,4-linked gluco-configured ligands. 相似文献
919.
Combined Phospholipid Biomarker-16S rRNA Gene Denaturing Gradient Gel Electrophoresis Analysis of Bacterial Diversity and Physiological Status in an Intertidal Microbial Mat 下载免费PDF全文
Laura Villanueva Antoni Navarrete Jordi Urmeneta David C. White Ricardo Guerrero 《Applied microbiology》2004,70(11):6920-6926
A combined lipid biomarker-16S rRNA gene denaturing gradient gel electrophoresis analysis was used to monitor changes in the physiological status, biomass, and microbial composition of a microbial mat. In the morning hours, an increase in the biomass of layers containing a high density of phototrophs and a decrease in the growth rate in the deep layers were observed. The combined approach also revealed differences in major groups of microorganisms, including green nonsulfur, gram-positive, and heterotrophic bacteria. 相似文献
920.
Anna Farag F. Antoni A. Takts F. Fbin 《Biochimica et Biophysica Acta (BBA)/General Subjects》1973,297(2):517-526
Human tonsillar lymphocytes were fractionated by a hypotonic extraction procedure, followed by the purification and extraction of nuclei. Two different histone kinases could be separated by DEAE-cellulose chromatography from the hypotonic extract, each of which phosphorylated the F2b histone fraction preferentially. In the nuclear extract, a third histone kinase fraction was found, which primarily phosphorylated the F2a histone. Only one of the histone kinases, found in the hypotonic extract, was cyclic AMP dependent, and the other two enzymes were independent of the cyclic nucleotide. In contrast with the other two histone kinases the cyclic AMP-dependent enzyme had a specific effect, phosphorylating mainly one particular site of the F2b histone fraction in the presence of cyclic AMP. 相似文献