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211.
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G Flouret W Brieher T Majewski K Mahan L Wilson 《International journal of peptide and protein research》1991,38(2):169-175
We synthesized 10 analogs (1-10) derived from the sequence of [Pmp1,D-Trp2,Arg8]oxytocin, (parent antagonist or PA), (Pmp = beta,beta-pentamethylene-beta-mercaptopropionic acid) which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as determined in our uterotonic assay. Eight of the following analogs were designed by replacement of each residue in the PA sequence, other than the residue at position 2, with D-tryptophan: Ac-D-Trp-D-Trp-Ile-Gln-Asn-Val-Pro- Arg-Gly-NH2, (1); [Pmp1,D-Trp(For)2,Arg8] OT, (2); [Pmp1,D-Trp2,D-Trp3,Arg8] OT, (3); [Pmp1,D-Trp2,D-Trp4,Arg8] OT, (4); [Pmp1,D-Trp2,D-Trp5,Arg8] OT, (5); Aaa-D-Trp-Ile-Gln-Asn-D-Trp-Pro-Arg- Gly-NH2, (6); [Pmp1,D-Trp2,D-Trp7,Arg8] OT, (7); [Pmp1,D-Trp2,D-Trp8] OT, (8); [Pmp1,D-Trp2,Arg8,D-Trp9] OT, (9); [Pmp1,D-Trp2,Arg8,D-Trp(For)9] OT, (10). To avoid free mercaptan groups, Val6 was chosen in analog 1 instead of Cys and Aaa1 (Aaa = 1-adamantaneacetic acid) in analog 6 instead of Pmp1. Of the linear analogs, 1 was inactive as an OT antagonist and 6 was a very poor antagonist, with a pA2 = 5.66, but it was more potent than Aaa-D-Trp-Ile-Gln-Asn-Val-Pro-Arg-Gly-NH2, which has a pA2 = 5.33, as we had previously reported. Analog 2, featuring D-Trp(For)2, pA2 = 7.37, was weaker than PA, indicating that the formyl group lowers potency. Analogs 3 and 4 were much weaker than PA, and analog 5 was inactive. Hence, other than at position 2, D-Trp is undesirable in the ring sequence of PA.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
214.
D J Donaldson M K Dunlap J T Mahan 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1984,79(2):243-248
Following removal of a skin patch from each hind limb of a series of adult newts, the limbs were explanted into small dishes of Holtfreter solution containing various combinations of test drugs. Later, the amount of wound epithelium that formed on each limb was determined using a planimeter on wound tracings obtained with the aid of a drawing tube-equipped microscope. Exposure of migrating cells to the plant lectin, concanavalin A (con A), lowered cyclic AMP (cAMP) levels and depressed migration. Exposure to cholera toxin and theophylline (CTX) significantly elevated cAMP levels and significantly depressed migration rate. Exposure of CTX-treated cells to con A tended to lower CTX-elevated cAMP levels while depressing the migration rate well beyond the depression caused by CTX alone. These results provide further evidence that cAMP can regulate the rate of newt epidermal cell migration. They also show that the inhibitory effect of con A on motility in these cells is independent of its effects on cAMP. 相似文献
215.
Deepti Lall Ileana Lorenzini Thomas A. Mota Shaughn Bell Thomas E. Mahan Jason D. Ulrich Hayk Davtyan Jessica E. Rexach A.K.M. Ghulam Muhammad Oksana Shelest Jesse Landeros Michael Vazquez Junwon Kim Layla Ghaffari Jacqueline Gire O’Rourke Daniel H. Geschwind Mathew Blurton-Jones David M. Holtzman Robert H. Baloh 《Neuron》2021,109(14):2275-2291.e8
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217.
Adenocarcinoma of the prostate is responsible for one of every nine deaths from cancer in Canada. In this review epidemiologic factors are considered and current staging systems are outlined. The American Urological System is recommended for staging because of its ability to reflect changes in the understanding of the biologic behaviour of this neoplasm. The adoption of a quantitative grading scheme is suggested to complement the information obtained from the staging assessment. The routes of spread of this disease, along with the procedures used to assess metastatic involvement, are described. Immunologic methods for the analysis of prostatic acid phosphatase have been shown to be superior to the enzymatic methods previously used, and the role of the new techniques is discussed. Emphasis is placed on radiotherapy and endocrine therapy for the treatment of this neoplasm, and the concept of withholding endocrine therapy until symptoms appear is discussed. Potential future developments in this field are considered. 相似文献
218.
Developing taste buds in the anterior mandibular floor of perihatching
chicks were studied by high voltage electron microscopic autoradiography in
order to identify proliferating gemmal cell types. Montaged profiles of 29
taste buds in five cases euthanized between embryonic day 21 and
posthatching day 2 were analyzed after a single [3H]thymidine injection
administered on embryonic day 16, 17 or 18. Results showed that dark cells
comprised 55% of identified (n = 900 cells) and 62% of labeled (n = 568
cells) gemmal cells as compared with light, intermediate, basal or
perigemmal bud cells. Dark cells had both a greater (P < 0.05) number of
labeled cells and a greater amount of label (grains/nucleus) than the other
four bud cell types, irrespective of injection day. The nuclear area
(micron 2) of dark cells was not significantly larger (P > 0.05) than
that of the other gemmal cell types and therefore cannot account for the
greater amount for label in the dark cells. Interestingly, only dark cells
showed a positive correlation (P < 0.003) between amount of label and
nuclear area. Results suggest that, during the perihatching period of
robust cell proliferation, dividing dark cells may give rise primarily, but
not exclusively, to dark cell progeny.
相似文献
219.
Sequence and functional differences between Schmidt-Ruppin D and Schmidt-Ruppin A strains of pp60v-src. 总被引:1,自引:0,他引:1 下载免费PDF全文
We show that Schmidt-Ruppin D pp60v-src kinase activity is reduced by a mutation previously shown to be associated with Schmidt-Ruppin A pp60v-src temperature sensitivity and that its reduced transforming activity is associated with a conformational change in the SH3 region. The evolutionary relationship of seven v-src strains was studied by using parsimony analysis. 相似文献