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排序方式: 共有236条查询结果,搜索用时 156 毫秒
161.
Richard L. Tolman Soumya P. Sahoo Raman K. Bakshi Dominick Gratale Gool Patel Sushma Patel Jeffrey Toney Benedict Chang Georgianna S. Harris 《The Journal of steroid biochemistry and molecular biology》1997,60(5-6)
4-Aza-5α-androstan-3-one 17β-(N-substituted carboxamides) are potent human type 2 5α-reductase (5aR) inhibitors with generally poor binding to the human androgen receptor (hAR). When the 17-amide N-substituent included an aromatic residue, potent dual inhibitors of both type 1 and 2 5aR are produced, but hAR binding remained poor. Tertiary-substituted-17-amides have reduced inhibition of both 5aR isozymes. The addition of an N4-methyl substitutent to the A-ring profoundly increased hAR affinity and the addition of unsaturation to the A-ring (Δ1) modestly augmented hAR binding. The unsubstituted carbanilides in the Δ1-N4-methyl series show some selectivity for type 1 5aR over the type 2 isozyme, whereas addition of aryl substituents, particularly at the 2-position, increased type 2 5aR binding to provide dual inhibitors with excellent hAR binding, e.g. N-(2-chlorophenyl)-3-oxo-4-methyl-4-aza-5α-androst-1-ene-17β-carboxamide (9c). Compounds of this type exhibit low nanomolar IC50s for both human 5aR isozymes as well as the human androgen receptor. Kinetic analysis confirms that the prototype 9c displays reversible, competitive inhibition of both human isozymes of 5aR with Ki values of less than 10 nM. Furthermore, this compound binds to the androgen receptor with an IC50 equal to 8 nM. Compounds in this series are projected to be powerful antagonists of testosterone and dihydrotestosterone action in vivo, with potential utility in the treatment of prostatic carcinoma (PC). 相似文献
162.
Thomas M. Shinnick Dominick J. Pallotta Y'Vonne R. Jones-Brown Philip J. Youngman Charles E. Holt 《Current microbiology》1978,1(3):163-166
Mating inPhysarum polycephalum involves the fusion of two haploid amoebae and the differentiation of the resulting diploid zygote into a multinucleate plasmodium.
Mating proceeds optimally with amoebae growing on an agar medium at pH 5.0. At pH 6.2, the amoebae still grow normally, but
mating is completely blocked. The barrier at pH 6.2 is not in the differentiation step, since preformed diploids readily convert
to plasmodia at this pH. The barrier can be overcome by raising the ionic strength of the agar medium; the effect, moreover,
is not ion-specific. We have discovered a genetic locus,imz (ionicmodulation of zygote formation), that affects the upper pH limit for mating; the respective limits associated with the two
known alleles,imz-1 andimz-2, are pH 5.6 and pH 6.0 at low ionic strength. Animz-1×imz-2 mating displays the pH 6.0 limit;imz-2 is therefore “dominant”. We suggest that this new gene affects a cell component that is exposed to the exterior of the amoeba
and is involved in the fusion step of mating. 相似文献
163.
Although microsomes prepared from rat kidney cortex contained significant concentrations of both NADH cytochrome b5 reductase and cytochrome b5, they did not catalyze cytochrome b5-dependent Δ9 oxidative lipid desaturation. However, incubation of kidney microsomes in the presence of control liver microsomes resulted in a two-fold increase in fatty acid desaturase activity over that seen with liver microsomes alone. Addition of kidney microsomes to liver microsomes prepared from animals maintained on a fat free diet resulted in an increased desaturase activity which was twice that seen with the control liver preparation. Kidney microsomes alone did not catalyze the cytochrome P-450-dependent N-demethylation of aminopyrine, and in contrast to the desaturate, no increase in demethylase activity was observed when kidney microsomes were added to liver microsomes. 相似文献
164.
A study of the interaction between ethidium bromide and rye chromatin: comparison with calf thymus chromatin. 总被引:1,自引:1,他引:0
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We studied the interaction of ethidium bromide with rye and calf thymus chromatin. Both types of chromatin have the same dye accessibility, which is about 50% of that of DNA. From this result we conclude that the molecular structure of these two chromatins is similar. For rye, the extraction of H1 produces no change in the binding of ethidium bromide. The subsequent extraction of H2A and H2B produces a 14% increase in the binding, and the removal of H3 and H4, another 54% increase. At this stage, the number of binding sites is still less than that of DNA. This is presumably due to the presence of some tightly bound non-histones. Thus, the arginine-rich histones and the tightly bound non-histones are most responsible for limiting the binding of ethidium bromide to rye chromatin. 相似文献
165.
A comparison of shoot apices of runners and rosettes of Nephrolepis with shoot apices of Adiantum indicates that a uniform concept of apical organization can be applied throughout. The region directly below the apical initials is designated a “central zone,” by analogy with that found in Lycopodium. The central zone is regarded as undifferentiated meristematic tissue rather than incipient vascular tissue. 相似文献
166.
167.
Profilin plays an important role in actin organization in all eukaryotic cells through mechanisms that are still poorly understood. We had previously shown that Mid2p, a transmembrane protein and a potential cell wall sensor, is an effective multicopy suppressor of the profilin-deficient phenotype in Saccharomyces cerevisiae. To better understand the role of Mid2p in the organization of the actin cytoskeleton, we isolated five additional multicopy suppressors of pfy1Delta cells that are Rom1p, Rom2p, Rho2p, Smy1p, and the previously uncharacterized protein Syp1p. The problems of caffeine and NaCl sensitivity, growth defects at 30 degrees and 37 degrees, the accumulation of intracellular vesicular structures, and a random budding pattern in pfy1Delta cells are corrected by all the suppressors tested. This is accompanied by a partial repolarization of the cortical actin patches without the formation of visible actin cables. The overexpression of Mid2p, Rom2p, and Syp1p, but not the overexpression of Rho2p and Smy1p, results in an abnormally thick cell wall in wild-type and pfy1Delta cells. Since none of the suppressors, except Rho2p, can correct the phenotype of the pfy1-111/rho2Delta strain, we propose a model in which the suppressors act through the Rho2p signaling pathway to repolarize cortical actin patches. 相似文献
168.
169.
Distinct roles of immunoreceptor tyrosine‐based motifs in immunosuppressive indoleamine 2,3‐dioxygenase 1
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Marco Gargaro Giada Mondanelli Maria L. Belladonna Maria Teresa Pallotta Claudia Volpi Francesca Fallarino Antonio Macchiarulo Cinzia Antognelli Roberta Bianchi Carmine Vacca Paolo Puccetti Ursula Grohmann Ciriana Orabona 《Journal of cellular and molecular medicine》2017,21(1):165-176
The enzyme indoleamine 2,3‐dioxygenase 1 (IDO1) catalyses the initial, rate‐limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation and the production of immunoregulatory kynurenines. IDO1's catalytic function has long been considered as the one mechanism responsible for IDO1‐dependent immune suppression by dendritic cells (DCs), which are master regulators of the balance between immunity and tolerance. However, IDO1 also harbours immunoreceptor tyrosine‐based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated, bind protein tyrosine phosphatases, (SHP‐1 and SHP‐2), and thus trigger an immunoregulatory signalling in DCs. This mechanism leads to sustained IDO1 expression, in a feedforward loop, which is particularly important in restraining autoimmunity and chronic inflammation. Yet, under specific conditions requiring that early and protective inflammation be unrelieved, tyrosine‐phosphorylated ITIMs will instead bind the suppressor of cytokine signalling 3 (SOCS3), which drives IDO1 proteasomal degradation and shortens the enzyme half‐life. To dissect any differential roles of the two IDO1's ITIMs, we generated protein mutants by replacing one or both ITIM‐associated tyrosines with phospho‐mimicking glutamic acid residues. Although all mutants lost their enzymic activity, the ITIM1 – but not ITIM2 mutant – did bind SHPs and conferred immunosuppressive effects on DCs, making cells capable of restraining an antigen‐specific response in vivo. Conversely, the ITIM2 mutant would preferentially bind SOCS3, and IDO1's degradation was accelerated. Thus, it is the selective phosphorylation of either ITIM that controls the duration of IDO1 expression and function, in that it dictates whether enhanced tolerogenic signalling or shutdown of IDO1‐dependent events will occur in a local microenvironment. 相似文献
170.
Nutrient concentration-stream discharge relationships during storm events in a first-order stream 总被引:1,自引:1,他引:1
Wayne F. McDiffett Andrew W. Beidler Thomas F. Dominick Kenneth D. McCrea 《Hydrobiologia》1989,179(2):97-102
The relationship between nutrient element concentration and stream discharge during storm events was studied in a nutrient-rich first order stream. Stream concentrations of NO3-N, phosphate-P, Ca, and Mg were determined during the course of and following thunderstorms. Nutrient element trajectories were constructed for the elements monitored and some recognizable and reproducible patterns in nutrient concentrations emerged. NO3-N and phosphate-P generally increased in concentration during the early stages of increasing stream discharge resulting in a general clockwise trajectory. Ca and Mg consistently showed decreases in concentration during rising water, but the pattern of the trajectories was less constant. The patterns seen for NO3-N and phosphate-P suggest surface run-off as their origin while the patterns for Ca and Mg reflect their primary origin in groundwater. The ability to detect these differences from the analysis of nutrient trajectories suggests the use of this technique for determining the source of other elements in streams. 相似文献