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91.
Avian thyroid development in chemically contaminated environments: is there evidence of alterations in thyroid function and development? 总被引:1,自引:0,他引:1
Poor reproductive success, developmental abnormalities, and behavioral alterations in fish-eating birds in some Great Lakes areas have led to more than 35 years of toxicological studies and residue monitoring of herring gull (Larus argentatus) populations. Polyhalogenated aromatic hydrocarbons (PHAHs), especially polychlorinated biphenyls (PCBs), are widespread contaminants in the Great Lakes ecosystem. The introduction of regulations and elimination of point sources since the 1970s have resulted in decreased PHAHs in fish-eating bird eggs and tissues. PCB exposure is associated with thyroid disruption (hypothyroidism) in mammals, but much less is known of PCB effects on avian thyroid function. Our 1998-2000 studies of herring gulls from the Great Lakes show that both pipping embryos and prefledglings from highly contaminated sites have marked depletion of thyroid gland hormone stores compared with similarly aged gulls at the reference sites. However, organismal hypothyroidism was not apparent in many embryo and chick collections where severe depletion of thyroid gland hormone was observed. Adults, sampled at two high PCB sites and a low PCB site in the Great Lakes and the maritime reference colony in 2001, showed no differences in organismal thyroid status across sites, but gulls from the high sites had enlarged thyroid glands and depressed thyroid gland hormone stores. Here we discuss the evidence that ecological exposure to PHAHs are responsible for thyroid deficiencies in gulls and that during development these deficiencies lead to developmental abnormalities in young gulls from highly contaminated Great Lakes sites. 相似文献
92.
93.
MacDonell LE Skinner FK Ward PE Glen AI Glen AC Macdonald DJ Boyle RM Horrobin DF 《Prostaglandins, leukotrienes, and essential fatty acids》2000,63(1-2):37-39
Research findings are increasingly reporting evidence of physiological abnormalities in dyslexia and sites for dyslexia have been identified on three chromosomes. It has been suggested that genetic inheritance may cause phospholipid abnormalities in dyslexia somewhat similar to those found in schizophrenia. A key enzyme in phospholipid metabolism, Type IV, or cytosolic, phospholipase A2 (cPLA2), releases arachidonic acid (AA), a 20-carbon fatty acid, which is the major source of production of prostaglandins and leukotrienes. An entirely new assay, which for the first time has enabled determination of the amount of the enzyme rather than its activity, was used to measure cPLA2 in dyslexic-type adults and controls and the two groups were found to differ significantly, the dyslexic-types having more of the enzyme. A report elsewhere of schizophrenics having even greater amounts of the enzyme suggests that dyslexia may be on a continuum with schizophrenia, as may be other neurodevelopmental disorders - which have also been described as phospholipid spectrum disorders. 相似文献
94.
95.
Receptor-ligand interactions have traditionally been evaluated using a number of biochemical techniques including radioligand binding, photoaffinity labeling, crosslinking, and chemical modification. In modern biochemistry, these approaches have largely been superseded by site-directed mutagenesis in the study of protein function, owing in part to a better understanding of the chemical properties of oligonucleotides and to the ease with which mutant clones can now be generated. The Altered Sites II in vitro Mutagenesis System from the Promega Corporation employs oligonucleotides containing two mismatches to introduce specific nucleotide substitutions in the nucleic acid sequence of a target DNA. One of these mismatches will alter the primary sequence of a given protein, whereas the second will give rise to a silent restriction site that is used to screen for mutants. Transient transfection of tsA201 cells with mutant cDNA constructs using calcium phosphate as a carrier for plasmid DNA permits expression of recombinant receptors that can be characterized using radioligand binding assays. In this article, we focus on site-directed mutagenesis, heterologous expression in eukaryotic cells, and radioligand binding as a methodology to enable the characterization of receptor-ligand interactions. 相似文献
96.
Boyle GM Roucou X Nagley P Devenish RJ Prescott M 《Journal of bioenergetics and biomembranes》2000,32(6):595-607
We have sought to elucidate how the oligomycin sensitivity-conferring protein (OSCP) of the mitochondrial F1F0-ATP synthase (mtATPase) can influence proton channel function. Variants of OSCP, from the yeast Saccharomyces cerevisiae, having amino acid substitutions at a strictly conserved residue (Gly166) were expressed in place of normal OSCP. Cells expressing the OSCP variants were able to grow on nonfermentable substrates, albeit with some increase in generation time. Moreover, these strains exhibited increased sensitivity to oligomycin, suggestive of modification in functional interactions between the F1 and F0 sectors mediated by OSCP. Bioenergetic analysis of mitochondria from cells expressing OSCP variants indicated an increased respiratory rate under conditions of no net ATP synthesis. Using specific inhibitors of mtATPase, in conjunction with measurement of changes in mitochondrial transmembrane potential, it was revealed that this increased respiratory rate was a result of increased proton flux through the F0 sector. This proton conductance, which is not coupled to phosphorylation, is exquisitely sensitive to inhibition by oligomycin. Nevertheless, the oxidative phosphorylation capacity of these mitochondria from cells expressing OSCP variants was no different to that of the control. These results suggest that the incorporation of OSCP variants into functional ATP synthase complexes can display effects in the control of proton flux through the F0 sector, most likely mediated through altered protein—protein contacts within the enzyme complex. This conclusion is supported by data indicating impaired stability of solubilized mtATPase complexes that is not, however, reflected in the assembly of functional enzyme complexes in vivo. Given a location for OSCP atop the F1-33 hexamer that is distant from the proton channel, then the modulation of proton flux by OSCP must occur at a distance. We consider how subtle conformational changes in OSCP may be transmitted to F0. 相似文献
97.
Glen P. Rosini Kun Wang Bhushan Patel Alan S. Goldman 《Inorganica chimica acta》1998,270(1-2):537-542
The thermolysis of trans-IrL2(CO)Cl(H)(C6H5) (1abd; L=P(i-Pr)3; H trans to CO) produces benzene and the Vaska-type complex IrL2(CO)Cl. A mechanistic study of the reaction has shown that 1a reversibly loses CO at 120 °C (as evidenced by the incorporation of 13CO) and isomerizes to the previously unreported 1b (H trans to Cl). It was found that 1b is the complex primarily responsible for the formation of benzene upon thermolysis under CO atmosphere; direct loss of benzene from 1a was determined to be, at most, a minor pathway. Benzaldehyde was also formed as a product of thermolysis of 1a under CO atmosphere. The first-order rate constant for benzene elimination in the absence of CO was found to be 8.5 × 10−5 s−1. The presence of only 5 Torr CO results in a decrease to 2.0 × 10−5 s−1, but little further inhibition is observed above 5 Torr CO. Added dihydrogen (100 Torr) was found to effect a novel catalysis of benzene elimination from 1a in the absence of CO atmosphere; it is suggested that trace amounts of dihydrogen, present in solutions of 1a, are responsible for the enhanced rate of elimination in the absence of CO. The thermolysis of 1-d6 in toluene was found to proceed without any toluene incorporation, implying that arene loss is irreversible. 相似文献
98.
Informative missingness of parental genotype data occurs when the genotype of a parent influences the probability of the parent's genotype data being observed. Informative missingness can occur in a number of plausible ways and can affect both the validity and power of procedures that assume the data are missing at random (MAR). We propose a bootstrap calibration of MAR procedures to account for informative missingness and apply our methodology to refine the approach implemented in the TRANSMIT program. We illustrate this approach by applying it to data on hypertensive probands and their parents who participated in the Framingham Heart Study. 相似文献
99.
Jitesh R. Shah Philip D. Mosier Bryan L. Roth Glen E. Kellogg Richard B. Westkaemper 《Bioorganic & medicinal chemistry》2009,17(18):6496-6504
Histamine H1 and serotonin 5-HT2A receptors present in the CNS have been implicated in various neuropsychiatric disorders. 9-Aminomethyl-9,10-dihydroanthracene (AMDA), a conformationally constrained diarylalkyl amine derivative, has affinity for both of these receptors. A structure–affinity relationship (SAFIR) study was carried out studying the effects of N-methylation, varying the linker chain length and constraint of the aromatic rings on the binding affinities of the compounds with the 5-HT2A and H1 receptors. Homology modeling of the 5-HT2A and H1 receptors suggests that AMDA and its analogs, the parent of which is a 5-HT2A antagonist, can bind in a fashion analogous to that of classical H1 antagonists whose ring systems are oriented toward the fifth and sixth transmembrane helices. The modeled orientation of the ligands are consistent with the reported site-directed mutagenesis data for 5-HT2A and H1 receptors and provide a potential explanation for the selectivity of ligands acting at both receptors. 相似文献
100.
Danijel Tosovic Estifanos Ghebremedhin Christopher Glen Mark Gorelick J. Mark Brown 《Journal of electromyography and kinesiology》2012,22(6):930-938
Although critical for effective human locomotion and posture, little data exists regarding the segmentation, architecture and contraction time of the human intrinsic foot muscles. To address this issue, the Abductor Hallucis (AH), Abductor Digiti Minimi (ADM), Flexor Digitorum Brevis (FDB) and Extensor Digitorum Brevis (EDB) were investigated utilizing a cadaveric dissection and a non-invasive whole muscle mechanomyographic (wMMG) technique. The segmental structure and architecture of formaldehyde-fixed foot specimens were determined in nine cadavers aged 60–80 years. The wMMG technique was used to determine the contraction time (Tc) of individual muscle segments, within each intrinsic foot muscle, in 12 volunteers of both genders aged between 19 and 24 years.While the pattern of segmentation and segmental –architecture (e.g. fibre length) and –Tc of individual muscle segments within the same muscle were similar, they varied between muscles. Also, the average whole muscle Tc of FDB was significantly (p < 0.05) shorter (faster) (Tc = 58 ms) than in all other foot muscles investigated (ADM Tc = 72 ms, EDB Tc = 72 ms and ABH Tc = 69 ms). The results suggest that the architecture and contraction time of the FDB reflect its unique direct contribution, through toe flexion, to postural stability and the rapid development of ground reaction forces during forceful activities such as running and jumping. 相似文献