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181.
The heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ),
2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-
6-phenylimidazo[4,5-b]pyridine (PhIP) are pyrolysis products formed when
meat is cooked and are rodent mammary carcinogens. They are thought to be
metabolically activated by N-hydroxylation, catalysed by cytochrome P450
(CYP), followed by O-acetylation catalysed by N- acetyltransferases.
Primary cultures of human mammary epithelial cells (HMECs) prepared from up
to 26 individuals for each compound, were treated with IQ, MeIQ, or PhIP
(500 microM) or with N-hydroxy-2-amino-1-
methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) or N-hydroxy-2-amino-
3-methylimidazo[4,5-f]quinoline (N-OH-IQ) (20 microM) and the levels of
adduct formation in their DNA analysed by 32P-post-labelling. In order to
investigate whether pharmacogenetic polymorphisms influence DNA adduct
formation, the NAT2 genotype of each individual was determined by a
polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) method that distinguishes between the wild-type and four variant
alleles. Presence of two variant alleles designates a slow NAT2 acetylator,
whereas individuals with one or two wild-type alleles are designated fast
NAT2 acetylators. Interindividual variations in total DNA adduct levels
ranged for IQ from 0.64-63.1 DNA adducts per 10(8) nucleotides (mean 7.80),
for MeIQ from 1.99-17.8 (mean 6.63), for PhIP from 0.13-4.0 (mean 0.96),
for N-OH-PhIP from 6.32-497 (mean 176) and for N-OH-IQ from 0.92-30.6 (mean
9.24). The higher adduct levels observed in cells treated with the N-OH
metabolites suggests that N- hydroxylation is the rate-limiting step in
HMECs and this may be due to low CYP levels. In contrast, the Phase II
reaction catalysed by N- acetyltransferases is probably the major step in
the metabolic activation of heterocyclic amines that occurs in the breast.
Higher mean levels of heterocyclic amine-DNA adduct formation were detected
in the cells of NAT2 fast acetylators compared with slow acetylators, with
mean adduct levels per 10(8) nucleotides following IQ treatment, of 12.74
and 3.57 respectively, following PhIP treatment, of 1.20 and 0.74,
respectively, following MeIQ treatment, of 7.90 and 5.08, respectively and
following N-OH-PhIP-treatment, of 243.1 and 130.0, respectively. However,
due to the large variations in adduct levels, these differences in mean
values were not statistically significant with the limited number of
individuals studied. This appears to be the first pilot study to
demonstrate interindividual variations in the metabolic activation of
heterocyclic amines and their metabolic intermediates in primary cultures
of HMECs in vitro.
相似文献
182.
183.
本文报告了一种敏感、简单、重复性好、成功率高的非放射性同位素法测定抗细菌性单抗的靶抗原的分子量的技术。此法综合了生物素标记细胞表面抗原、固相免疫分离法、SDS-PAGE、免疫印染法和增强的化学发光检测系统等优点,并成功测定了一组抗Ewing氏肉瘤等单克 隆抗体相应的细胞表面靶分子的分子量。 相似文献
184.
The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture 总被引:12,自引:5,他引:12
Laird SM; Tuckerman EM; Dalton CF; Dunphy BC; Li TC; Zhang X 《Human reproduction (Oxford, England)》1997,12(3):569-574
The concentration of leukaemia inhibitory factor (LIF) was measured in
uterine flushings obtained from normal fertile women, from women with
unexplained infertility and from women who suffered recurrent miscarriage.
In normal fertile women, LIF was not detected in flushings obtained on days
luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations
gradually increased from day LH+7 to a maximum at day LH+12. The amount of
LIF in flushings obtained from women with unexplained infertility was
significantly lower than in those from normal fertile women on day LH+10 (P
< 0.05). The production of LIF by cultured human epithelial and stromal
cells was also investigated. LIF was not detectable in the supernatants of
cultured stromal cells. Basal LIF production by epithelial cells varied
according to the stage in the cycle at which the biopsy was taken.
Significantly more LIF was produced by epithelial cells from late
proliferative and early secretory endometrium compared with amounts
produced by cells from early proliferative (P < 0.001) and late
secretory (P < 0.01) endometrium. High doses of progesterone and
oestradiol caused a small decrease in epithelial cell LIF production: the
combined effect of progesterone and oestradiol (P < 0.01) was greater
than the effect of either steroid alone (P < 0.05). The results show,
for the first time, the capability of human endometrium to produce LIF in
vivo. The fact that maximum LIF concentrations are present at implantation
and that decreased concentrations occur in women with unexplained
infertility suggest the importance of this cytokine in embryo implantation.
相似文献
185.
Kaaijk EM; Beek JF; Hamerlynck JV; van der Veen F 《Human reproduction (Oxford, England)》1997,12(11):2370-2372
We performed unilateral oophorectomy (UO) in three patients with polycystic
ovary syndrome (PCOS) and long-standing infertility. The indication for
performing this procedure was a combination of ovarian pathology and the
long-standing infertility. All three patients were resistant to clomiphene
citrate and before UO all patients had been treated unsuccessfully with
gonadotrophins and in-vitro fertilization. All three patients became
ovulatory within the first month after UO. Two patients conceived 11 and 12
months after surgery respectively and delivered healthy babies.
Testosterone concentrations decreased in two patients to upper values of
the normal range and remained unchanged in one patient. We conclude that
restoration of ovulation can be a beneficial side-effect of UO in
clomiphene citrate resistant patients with PCOS and long-standing
infertility.
相似文献
186.
Summary The fetal heart was studied with transabdominal sonography in 40 single normal pregnancies to analyze the increase of cardiac length and width (major longitudinal and transverse diameters of the heart) during the third trimester. Relationships between the cardiac data and fetal age, femur length and biparietal diameter (BPD) were explored by allometry and linear regression analysis. The length and width of the heart could be measured reproducibly in the 4-chamber view of the heart. This study verified that the heart grows very rapidly during the third trimester (positive allometry). The linear increase of the fetal heart shows a strong and significant correlation with the increase of both femur length and BPD. This suggests that non invasive analysis of cardiac data can be useful for prenatal detection of congenital heart disease or for the assessment of gestational age.This work was supported by the Brazilian agency CNPq (Grant number 50.00.427/91-7) 相似文献
187.
188.
Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E) 总被引:7,自引:3,他引:7
Bonnemann CG; Passos-Bueno MR; McNally EM; Vainzof M; de Sa Moreira E; Marie SK; Pavanello RC; Noguchi S; Ozawa E; Zatz M; Kunkel LM 《Human molecular genetics》1996,5(12):1953-1961
Autosomal recessive limb-girdle muscular dystrophies (LGMDs) are
genetically heterogeneous. A subgroup of these disorders is caused by
mutations in the dystrophin-associated sarcoglycan complex. Truncating
mutations in the 43 kDa beta-sarcoglycan gene (LGMD 2E) were originally
identified in a sporadic case of Duchenne-like muscular dystrophy, and a
common missense mutation (T151R) was identified independently in Indiana
Amish pedigrees with a milder form of LGMD. To facilitate mutational
analysis of larger numbers of patients directly from genomic DNA, as
opposed to reverse transcribed RNA from muscle biopsies, we have determined
the genomic structure of the beta-sarcoglycan gene. The open reading frame
of the beta-sarcoglycan coding region extends over six exons. Primers were
designed for PCR amplification of single exons from genomic DNA and
subsequent single strand conformation polymorphism (SSCP) analysis. We
screened 15 patients from the Brazilian LGMD patient population, 13 of whom
followed a severe course. Most of the patients had been assessed previously
for deficiency of alpha- sarcoglycan immunofluorescence on muscle biopsy
sections as a marker for disease of the sarcoglycan complex. Novel
mutations in two familial and two sporadic cases of severe childhood-onset
LGMD were identified. Only one of these patients carried a truncating
mutation (homozygous 2 bp deletion, FS164TER), while the other three
carried missense mutations (homozygous R91P, homozygous M100K, heterozygous
recessive L108R; only one allele could be identified in this family). All
three missense mutations occurred in exon 3, coding for the immediate
extracellular domain. Complete absence for all three of the known
sarcoglycans was noted by immunohistochemistry on muscle biopsy sections of
the patients.
相似文献
189.
Follistatin and activin A in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy 总被引:2,自引:0,他引:2
Riley SC; Balfour C; Wathen NC; Chard T; Evans LW; Groome NP; Wallace EM 《Human reproduction (Oxford, England)》1998,13(9):2624-2628
Follistatin is a specific binding protein which controls bioavailability of
activins and inhibins which have an important role in fetal development. In
the first trimester of pregnancy bioactive dimeric inhibins are found at
high concentrations in the extra- embryonic coelomic fluid, but the
distribution of follistatin and activins is not known. We have used
recently developed immunoassays for follistatin, activin A and activin AB
to determine their presence in the intrauterine compartments during early
pregnancy. Follistatin was present in highest concentrations in the
extra-embryonic coelomic fluid (11.72 +/- 1.70 ng/ml; median +/- SEM), with
less in maternal serum (6.35 +/- 4.58) and lowest amounts in amniotic fluid
(0.97 +/- 0.52). Follistatin concentrations in extra-embryonic coelomic
fluid were highly correlated with both dimeric inhibin isoforms. Activin A
was present in only barely detectable amounts in some samples of extra-
embryonic coelomic fluid (41% of samples) and maternal serum (26%) and was
undetectable in all amniotic fluid samples. Activin AB was undetectable in
all compartments. The presence of follistatin in the amniotic and
extra-embryonic coelomic fluids may regulate the availability of bioactive
activins and inhibins which are released into the intrauterine compartments
during the development of the fetus and placenta in early pregnancy.
相似文献
190.
JAJM van den Hurk M Schwartz H van Bokhoven TJR van de Pol L Bogerd AJLG Pinckers EM Bleeker-Wagemakers IH Pawlowitzki K Rüther H-H Ropers FPM Cremers 《Human mutation》1997,9(2):110-117
Choroideremia (CHM) is an X-linked recessive eye disease that results from mutations involving the Rab escort protein-1 (REP-1) gene. In 18 patients deletions of different sizes have been found. Two females suffering from CHM were reported to have translocations that disrupt the REP-1 gene. In 22 patients, small mutations have been identified. Interestingly, these are all nonsense, frameshift or splice-site mutations; with one possible exception, missense mutations have not been found. This comprises all the known mutations in the disease. Hum Mutat 9:110–117, 1997. © 1997 Wiley-Liss, Inc. 相似文献