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61.
Erica B. Sneider Philip T. Nowicki Louis M. Messina 《Journal of cellular biochemistry》2009,108(4):753-761
The last decade has witnessed a dramatic increase in the mechanistic understanding of angiogenesis and arteriogenesis, the two processes by which the body responds to obstruction of large conduit arteries. This knowledge has been translated into novel therapeutic approaches to the treatment of peripheral arterial disease, a condition characterized by progressive narrowing of lower extremity arteries and heretofore solely amenable to surgical revascularization. Clinical trials of molecular, genetic, and cell‐based treatments for peripheral artery obstruction have generally provided encouraging results. J. Cell. Biochem. 108: 753–761, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
62.
The colinear, anterior to posterior expression domains of theHox genes in vertebrate embryos is strongly correlated withregional changes in vertebral morphology. The limbs of tetrapodsare consistently aligned with specific areas of the vertebralcolumn. However, control of limb development is apparently situatedin the lateral plate mesoderm, and has been experimentally shownto be independent of an axial Hox code (Cohn et al., 1997, Nature387:97101). We have used experimental manipulation ofchick embryos to test the causal role of Hox genes in patterningderivatives of the paraxial mesoderm. Hox expression in heterotopicallytransplanted segmental plate responds in a manner consistentwith a patterning role for these genes in the morphologicalbehavior of the transplants. Expression is maintained in dorsalparaxial regions where patterning is also intrinsic to the donorsite of the graft. However, expression is apparently lost insomite cells that migrate into the host lateral plate environmentand form appropriate host-level muscles. This arrangement couldenable increased plasticity in the evolution of transpositionalvariation in the vertebrate body plan. 相似文献
63.
Prognostic significance of Ki67-negative blast cell clone in the high risk group of children treated for acute myeloid leukaemia 总被引:1,自引:0,他引:1
Nowicki M Ostalska-Nowicka D Miśkowiak B 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2006,44(1):49-52
The aim of this study was to demonstrate the value of immunocytochemical staining of Ki67 antigen expression in blast cells of children with acute myeloid leukemia (AML) and to evaluate its correlation with treatment failure. The material included bone marrow specimens obtained during induction treatment from 46 children treated for AML between 1998-2003. Immunocytochemical staining for Ki67 was based on the ABC technique. Expression of Ki67 antigen on day 0 of induction treatment was confirmed in all patients. The percentage of immunopositive blasts ranged from 88.4% to 99.8% (mean 91.8%). On day 15, according to chemotherapy response, patients were divided into two groups: G1-36 children who responded to induction treatment and reached remission (blast level 5%, low risk group) and G2-10 patients who did not meet remission criterion (blast level > 5%) and were assigned to the high risk (HR) group. Out of 10 children assigned to this group, Ki67 expression in blast cells was confirmed in 4 cases. The fraction of immunopositive blasts ranged from 78.4% to 88.6%. In the other 6 cases, blasts were Ki67-negative. In 12-month period after beginning the treatment, 18 cases of treatment failure (including 7 deceases) were observed in both groups. Five deaths, observed in the HR group, concerned the patients characterized by Ki67-negative blasts. The results indicate a possible correlation between the Ki67-immunonegative blast pattern on day 15 of treatment induction and early decease of AML children assigned to HR group. 相似文献
64.
Matthew W. Nowicki Buabarn Kuaprasert Iain W. McNae Marjorie M. Harding Linda A. Fothergill-Gilmore 《Journal of molecular biology》2009,394(3):535-543
The structures of Leishmania mexicana cofactor-independent phosphoglycerate mutase (Lm iPGAM) crystallised with the substrate 3-phosphoglycerate at high and low cobalt concentrations have been solved at 2.00- and 1.90-Å resolutions. Both structures are very similar and the active site contains both 3-phosphoglycerate and 2-phosphoglycerate at equal occupancies (50%). Lm iPGAM co-crystallised with the product 2-phosphoglycerate yields the same structure. Two Co2+ are coordinated within the active site with different geometries and affinities. The cobalt at the M1 site has a distorted octahedral geometry and is present at 100% occupancy. The M2-site Co2+ binds with distorted tetrahedral geometry, with only partial occupancy, and coordinates with Ser75, the residue involved in phosphotransfer. When the M2 site is occupied, the side chain of Ser75 adopts a position that is unfavourable for catalysis, indicating that this site may not be occupied under physiological conditions and that catalysis may occur via a one-metal mechanism. The geometry of the M2 site suggests that it is possible for Ser75 to be activated for phosphotransfer by H-bonding to nearby residues rather than by metal coordination. The 16 active-site residues of Lm iPGAM are conserved in the Mn-dependent iPGAM from Bacillus stearothermophilus (33% overall sequence identity). However, Lm iPGAM has an inserted tyrosine (Tyr210) that causes the M2 site to diminish in size, consistent with its reduced metal affinity. Tyr210 is present in trypanosomatid and plant iPGAMs, but not in the enzymes from other organisms, indicating that there are two subclasses of iPGAMs. 相似文献
65.
66.
Anthony H Taylor Mark Finney Patricia MW Lam Justin C Konje 《Reproductive biology and endocrinology : RB&E》2011,9(1):1-18
Background
In early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA) are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua.Methods
In this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG), progesterone (P4) and (pregnancy-associated placental protein-A (PAPP-A)) essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels.Results
The median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20) was higher than in viable pregnancies (1.21 nM; n = 25; P = 0.013), as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; P = 0.052 for P4 and 28,650 vs 6,560 mIU/L; P = 0.144 for beta-hCG, respectively, but were not statistically significant). Serum PAPP-A levels in the viable group were approximately 6.8 times lower than those in the non-viable group (1.82 vs 12.25 mg/L; P = 0.071), but again these differences were statistically insignificant. In the spontaneous miscarriage group, significant correlations between P4 and beta-hCG, P4 and PAPP-A and AEA and PAPP-A levels were observed. Simultaneously, immunohistochemical distributions of the two main cannabinoid receptors and the AEA-modifying enzymes, fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), changed within both the decidua and trophoblast.Conclusions
The association of higher AEA levels with early pregnancy failure and with beta-hCG and PAPP-A, but not with progesterone concentrations suggest that plasma AEA levels and pregnancy failure are linked via a mechanism that may involve trophoblastic beta-hCG, and PAPP-A, but not, progesterone production. Although the trophoblast, decidua and embryo contain receptors for AEA, the main AEA target in early pregnancy failure remains unknown. 相似文献67.
SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children
68.
Zeigler MM Doseff AI Galloway MF Opalek JM Nowicki PT Zweier JL Sen CK Marsh CB 《The Journal of biological chemistry》2003,278(15):12894-12902
In the absence of survival factors, blood monocytes undergo spontaneous apoptosis, which involves the activation of caspase-3. Although nitric oxide can block caspase-3 activation and promote cell survival, it can also induce apoptosis. We hypothesized that nitrosothiols that promote protein S-nitrosylation would reduce caspase-3 activation and cell survival, whereas nitric oxide donors (such as 1-propamine 3-(2-hydroxy-2-nitroso-1-propylhydrazine (PAPA) NONOate and diethylamine (DEA) NONOate) that do not target thiol residues would not. Using human monocytes as a model, we observed that nitrosothiol donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine suppressed caspase-9 and caspase-3 activity and DNA fragmentation. In contrast, PAPA or DEA NONOate did not promote monocyte survival events and appeared to inhibit monocyte survival induced by macrophage colony-stimulating factor. The caspase-3-selective inhibitor DEVD-fluoromethyl ketone reversed DNA fragmentation events, and the caspase-9 inhibitor LEHD-fluoromethyl ketone reversed caspase-3 activity in monocytes treated with PAPA or DEA NONOate in the presence of macrophage colony-stimulating factor. These results were not caused by differences in glutathione levels or the kinetics of nitric oxide release. Moreover, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine directly blocked the activity of recombinant caspase-3, which was reversed by the reducing agent dithiothreitol, whereas PAPA or DEA NONOate did not block the enzymatic activity of caspase-3. These data support the hypothesis that nitrosylation of protein thiol residues by nitric oxide is critical for promoting the survival of human monocytes. 相似文献
69.
70.
Nowicki C Cazzulo JJ 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2008,151(3):381-390
Trypanosomatids cause important human diseases, like sleeping sickness, Chagas disease, and the leishmaniases. Unlike in the mammalian host, the metabolism of aromatic amino acids is a very simple pathway in these parasites. Trypanosoma brucei and Trypanosoma cruzi transaminate the three aromatic amino acids, the resulting 2-oxo acids being reduced to the corresponding lactate derivatives and excreted. In T. cruzi, two enzymes are involved in this process: a tyrosine aminotransferase (TAT), which despite a high sequence similarity with the mammalian enzyme, has a different substrate specificity; and an aromatic L-2-hydroxyacid dehydrogenase (AHADH), which belongs to the subfamily of the cytosolic malate dehydrogenases (MDHs), yet has no MDH activity. In T. cruzi AHADH the substitution of Ala102 for Arg enables AHADH to reduce oxaloacetate. In the members of the 2-hydroxyacid dehydrogenases family, the residue at this position is known to be responsible for substrate specificity. T. cruzi does not possess a cytosolic MDH but contains a mitochondrial and a glycosomal MDH; by contrast T. brucei and Leishmania spp. possess a cytosolic MDH in addition to glycosomal and mitochondrial isozymes. Although Leishmania mexicana also transaminates aromatic amino acids through a broad specificity aminotransferase, the latter presents low sequence similarity with TATs, and this parasite does not seem to have an enzyme equivalent to T. cruzi AHADH. Therefore, these closely related primitive eukaryotes have developed aromatic amino acid catabolism systems using different enzymes and probably for different metabolic purposes. 相似文献