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11.
Peter G.W. Plagemann Richard Marz Robert M. Wohlhueter Jon C. Graff John M. Zylka 《生物化学与生物物理学报:生物膜》1981,647(1):49-62
6-Mercaptopurine and 6-thioguanine strongly inhibited the zero-trans entry of hypoxanthine into Novikoff rat hepatoma cells which lacked hypoxanthine/guanine phosphoribosyltransferase, whereas 8-azaguanine had no significant effect. 6-Mercaptopurine was transported by the hypoxanthine carrier with about the same efficiency as its natural substrates (Michaelis-Menten constant = 372 ± 23 μM; maximum velocity = 30 ± 0.7 pmol/μl cell H2O per s). 8-Azaguanine entry into the cells, on the other hand, showed no sign of saturability and was not significantly affected by substrates of the hypoxanthine/guanine carrier. The rate of entry of 8-azaguanine at 10–100 μM amounted to only about 5% of that of hypoxanthine transport and was related to its lipid solubility in the same manner as observed for various substances whose permeation through the plasma membrane is believed to be non-mediated. Only the non-ionized form of 8-azaguanine (pKa = 6.6) permeated the cell membrane.Studies with wild type Novikoff cells showed that permeation into the cell was the main rate-determining step in the conversion of extracellular 8-azaguanine to intracellular aza-GTP and its incorporation into nucleic acids. In contrast, 6-mercaptopurine was rapidly transported into cells and phosphoribosylated; the main rate-determining step in its incorporation into nucleic acids was the further conversion of 6-mercaptopurine riboside 5'-monophosphate. 相似文献
12.
Thirteen new congenic lines have been produced which have chromosome-7 segments introduced from different strains onto the C57BL/10Sn background. Sublines B10.P(61NX)C,D, and E received chromosome-7 segments from P/J, B10.CE(62NX) from CE/J, B10.SEC(64NX)A,C,E, and F from SEC/1Re, B10.SM(65NX) from SM/J, B10.WB(66NX) from WB/Re, B10.A(67NX) from A/SnGrf, B10.AKR(68NX) from AKR/SnGrf, and B10.K(69NX) from C3H.K. Isograft testing indicated that three sublines, B10.P(61NX)D, B10.CE(62NX)B, and B10.WB(66NX)B are histoisogenic, i.e., histocompatible within each line. With the exception of B10.A(67NX), B10.AK(68NX), and B10.K(69NX), which have not been isografted, the remaining sublines showed residual heterozygosity on isografting. The three histoisogenic lines have undergone F1 testing and have been found to possess theH-4
a
allele and new and distinct alleles at theH-1 locus. They have been designated B10.P(61NX)-H-4a
H-1
d
, B10.WB(66NX)-H-4a
H-1
e
, and B10.CE(62NX)-H-4a
H-1
f
. Direct exchange of grafts has indicated the following genotypes: B10.A(67NX)-H-4a
H-1
b
, B10.AK(68NX)-H-4a
H-1
b
, and B10.K(69NX)-F-4a
H-1
b
. The B10.SEC(64NX) and B10.SM(65NX) sublines have not been typed completely forH-4 andH-1. F
1
testing or direct exchange of skin grafts indicated that B10.P(61NX)-H-4a
H-1
d
, B10.WB(66NX)-H-4a
H-1
e
, B10.A(67NX)-H-4a
H-1
b
B10.AK(68NX)-H-4a
H-1
b
and B10.K(69NX)-H-4a
H1
b
possess nonon-H-1 histocompatibility differences from the G57BL/10 background. 相似文献
13.
C Gueuning G L Graff C Dictus-Vermeulen 《Archives internationales de physiologie et de biochimie》1978,86(2):343-352
The subcutaneous injection of acrylamide (30 mg kg-1 day-1) in adult male rats induces a severe impairment of the general state of health and a progressive polyneuropathy at the cumulative dose of 180 mg/kg. At the cumulative dose of 400 mg acrylamide does not interfere with the incorporation of plasma inorganic phosphate into the inorganic and organic acid-soluble phosphate fractions of either the gastrocnemius muscle or the sciatic nerve Schwann cells. Nor does it modify the characteristic metabolic response of these fractions to Wallerian degeneration and neurogenic muscle atrophy. 相似文献
14.
15.
Hung-Hsin Chen Douglas M. Shaw Lauren E. Petty Misa Graff Ryan J. Bohlender Hannah G. Polikowsky Xue Zhong Daeeun Kim Victoria L. Buchanan Michael H. Preuss Megan M. Shuey Ruth J.F. Loos Chad D. Huff Nancy J. Cox Julie A. Bastarache Lisa Bastarache Kari E. North Jennifer E. Below 《American journal of human genetics》2021,108(1):194-201
16.
17.
Maria Wik Markhus Siv Skotheim Ingvild Eide Graff Livar Fr?yland Hanne Cecilie Braarud Kjell Morten Stormark Marian Kjellevold Malde 《PloS one》2013,8(7)
Background
Depression is a common disorder affecting 10–15% women in the postpartum period. Postpartum depression can disrupt early mother-infant interaction, and constitutes a risk factor for early child development. Recently, attention has been drawn to the hypothesis that a low intake of seafood in pregnancy can be a risk factor for postpartum depression. Seafood is a unique dietary source of the marine omega-3 fatty acids and is a natural part of a healthy balanced diet that is especially important during pregnancy.Methods
In a community based prospective cohort in a municipality in Western Norway, we investigated both nutritional and psychological risk factors for postpartum depression. The source population was all women who were pregnant within the period November 2009 - June 2011. The fatty acid status in red blood cells was assessed in the 28th gestation week and participants were screened for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) three months after delivery. The aim of the present study was to investigate if a low omega-3 index in pregnancy is a possible risk factor for postpartum depression.Results
In a simple regression model, the omega-3 index was associated with the EPDS score in a nonlinear inverse manner with an R square of 19. Thus, the low omega-3 index explained 19% of the variance in the EPDS score. The DPA content, DHA content, omega-3 index, omega-3/omega-6 ratio, total HUFA score, and the omega-3 HUFA score were all inversely correlated with the EPDS score. The EPDS scores of participants in the lowest omega-3 index quartile were significantly different to the three other omega-3 index quartiles.Conclusion
In this study population, a low omega-3 index in late pregnancy was associated with higher depression score three months postpartum. 相似文献18.
Alexandra M. Nicholson NiCole A. Finch Aleksandra Wojtas Matt C. Baker Ralph B. Perkerson III Monica Castanedes‐Casey Linda Rousseau Luisa Benussi Giuliano Binetti Roberta Ghidoni Ging‐Yuek R. Hsiung Ian R. Mackenzie Elizabeth Finger Bradley F. Boeve Nilüfer Ertekin‐Taner Neill R. Graff‐Radford Dennis W. Dickson Rosa Rademakers 《Journal of neurochemistry》2013,126(6):781-791
Frontotemporal lobar degeneration (FTLD) is the second leading cause of dementia in individuals under age 65. In many patients, the predominant pathology includes neuronal cytoplasmic or intranuclear inclusions of ubiquitinated TAR DNA binding protein 43 (FTLD‐TDP). Recently, a genome‐wide association study identified the first FTLD‐TDP genetic risk factor, in which variants in and around the TMEM106B gene (top SNP rs1990622) were significantly associated with FTLD‐TDP risk. Intriguingly, the most significant association was in FTLD‐TDP patients carrying progranulin (GRN) mutations. Here, we investigated to what extent the coding variant, rs3173615 (p.T185S) in linkage disequilibrium with rs1990622, affects progranulin protein (PGRN) biology and transmembrane protein 106 B (TMEM106B) regulation. First, we confirmed the association of TMEM106B variants with FTLD‐TDP in a new cohort of GRN mutation carriers. We next generated and characterized a TMEM106B‐specific antibody for investigation of this protein. Enzyme‐linked immunoassay analysis of progranulin protein levels showed similar effects upon T185 and S185 TMEM106B over‐expression. However, over‐expression of T185 consistently led to higher TMEM106B protein levels than S185. Cycloheximide treatment experiments revealed that S185 degrades faster than T185 TMEM106B, potentially due to differences in N‐glycosylation at residue N183. Together, our results provide a potential mechanism by which TMEM106B variants lead to differences in FTLD‐TDP risk.
19.
Ian W. Windsor Crystal J. Graff Ronald T. Raines 《Protein science : a publication of the Protein Society》2019,28(9):1713-1719
The endogenous production of enzymes as zymogens provides a means to control catalytic activities. Here, we describe the heterologous production of ribonuclease 1 (RNase 1), which is the most prevalent secretory ribonuclease in humans, as a zymogen. In folded RNase 1, the N and C termini flank the enzymic active site. By using intein‐mediated cis‐splicing, we created circular proteins in which access to the active site of RNase 1 is obstructed by an amino‐acid sequence that is recognized by the HIV‐1 protease. Installing a sequence that does not perturb the RNase 1 fold led to only modest inactivation. In contrast, the ancillary truncation of residues from each terminus led to a substantial decrease in the catalytic activity of the zymogen with the maintenance of thermostability. For optimized zymogens, activation by HIV‐1 protease led to a > 104‐fold increase in ribonucleolytic activity at a rate comparable to that for the cleavage of endogenous viral substrates. Molecular modeling indicated that these zymogens are inactivated by conformational distortion in addition to substrate occlusion. Because protease levels are elevated in many disease states and ribonucleolytic activity can be cytotoxic, RNase 1 zymogens have potential as generalizable prodrugs. 相似文献
20.
Aldi T. Kraja Chunyu Liu Jessica L. Fetterman Mariaelisa Graff Christian Theil Have Charles Gu Lisa R. Yanek Mary F. Feitosa Dan E. Arking Daniel I. Chasman Kristin Young Symen Ligthart W. David Hill Stefan Weiss Jian’an Luan Franco Giulianini Ruifang Li-Gao Fernando P. Hartwig Kari E. North 《American journal of human genetics》2019,104(1):112-138