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201.
Studies were performed to examine the mutational pattern of K-ras exons 1
and 2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese patients (10
smokers, 17 non-smokers) using single-stranded conformational polymorphism
and DNA sequencing. K-ras mutations were found in 13/27 tumors (48%); all
mutations were clustered in exon 1 and distributed between codons 9 and 32.
The frequency and number of patients with K-ras mutations between smokers
and non-smokers were not different, except that a high frequency of G
--> A transitions (11/11) was found in non-smokers. Among cell types,
K-ras mutations were found in 7/13 (54%) squamous cell carcinoma (SC) and
5/12 (42%) adenocarcinoma (AC) patients. A --> T transversions (all six
transversions) were present only in SC. In p53, 18/27 (67%) tumors
contained mutations in exons 7 and 8, frequently at codons 226, 270, 275
and 281. The number of tumors with p53 mutations in smokers (70%) and in
non-smokers (65%) was similar, and the mutation frequency did not differ
except for a higher number of G --> A (6/7) and T --> C (5/6)
transitions in non-smokers. Among cell types, the number of tumors with p53
mutations was 9/13 (69%) in SC and 8/12 (67%) in AC. The A --> G (11/16)
transitions and A --> C (4/4) transversions in p53 were more frequent in
SC than in AC (P < 0.04 for A --> G; P < 0.02 for A --> C). The
varying mutation patterns in both the K-ras and p53 genes between smokers
and non-smokers and among cell types suggest that other than cigarette
smoke, environmental and dietary factors may also be involved in the
genesis of lung cancer among these patients.
相似文献
202.
Lipoprotein(a) [Lp(a)] is a quantitative genetic trait in human plasma
associated with atherothrombotic disease. The major determinant of Lp(a)
concentration is the apolipoprotein(a) [apo(a)] gene locus. Variation in
the number of kringle IV repeats (K-IV VNTR) in apo(a) has a direct effect
on Lp(a) concentrations but explains only a fraction of the large intra-
and inter-population variance in Lp(a) levels. Effects on Lp(a) of other
intragenic polymorphisms including a pentanucleotide repeat (PNRP) in the
promoter likely reflect allelic associations with as yet unidentified
sequence variation in the apo(a) gene. We have studied a candidate C-->T
transition in two European and two African populations. This polymorphism
in the 5' region of the apo(a) gene creates an ATG start codon thereby
reducing apo(a) translation in vitro by 60%. All samples were also analyzed
for the K-IV VNTR and the PNRP to stratify for their effects and to
consider allelic associations. Consistent with the in vitro effect the
C-->T transition was associated with a significant reduction in Lp(a)
levels in both African populations ( P < 0.0056). In Caucasians,
however, the effect was not significant. This was explained by linkage
disequilibrium of the +93 T with apo(a) alleles of intermediate length
(K-24-K-34) and with nine PNRs. In Europeans these alleles are associated
with low Lp(a) which makes any potential effect of the +93 T undetectable
in the total sample. From our results we conclude (i) that the +93 C/T
polymorphism is the second known intragenic apo(a) polymorphism which
affects Lp(a) levels directly in vivo ; (ii) that allelic associations may
mask the effect of a mutation; and (iii) that heterogeneity of an effect of
a mutation across populations does not disprove causality.
相似文献
203.
Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome 总被引:5,自引:3,他引:5
Dalton CF; Laird SM; Estdale SE; Saravelos HG; Li TC 《Human reproduction (Oxford, England)》1998,13(11):3197-3202
The concentrations of endometrial proteins PP14 and CA-125 were measured in
uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after
luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile
women and 49 women who suffered recurrent miscarriage. The concentration of
PP14 was significantly lower in the flushings from the recurrent
miscarriage patients than in those from fertile controls on both day LH+10
(median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40
404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml
versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly
concentrations of CA-125 were significantly lower in flushings from
recurrent miscarriage women compared to controls on both day LH + 10
(median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731
U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus
median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there
was no significant difference in the concentration of PP14 in plasma
samples taken on the same days as the flushings from recurrent miscarriage
patients and fertile controls. The concentrations of PP14 in uterine
flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage
women during a pre-pregnancy investigative cycle were significantly lower
(P < 0.05) in patients who went on to miscarry (median: 1000, range:
9-2900 ng/ml) than those who went on to have a live birth (median: 1440,
range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was
no significant difference in uterine CA-125 or plasma PP14 concentrations
between these two groups of recurrent miscarriage patients. The results
suggest that measurements of uterine PP14 and CA-125 may be useful in the
assessment of endometrial development in recurrent miscarriage patients and
suggest the importance of PP14 in preparing the endometrium for embryo
implantation. In addition pre-pregnancy uterine PP14 measurements may be
useful in predicting subsequent pregnancy outcome.
相似文献
204.
Fazleabas AT; Donnelly KM; Hild-Petito S; Hausermann HM; Verhage HG 《Human reproduction update》1997,3(6):553-559
The biological function of uterine endometrial secretory proteinsin the primate remain to be elucidated. In general, during theluteal phase and under progesterone dominance, the glandularepithelial cells synthesize and secrete a number of proteins.Of these, placental protein 14 (PP14; now referred to as glycodelin)and insulin-like growth factor binding protein-1 (IGFBP-1) arethe best characterized. Although induced by progesterone, theirsynthesis increases exponentially during pregnancy. In the baboon,glycodelin is immunolocalized to the mid functionalis and basalglands between days 10 and 12 post-ovulation. In response toeither exogenous or blastocyst-secreted chorionic gonadotrophin,glandular synthesis increases markedly and remains elevatedup to days 18-25 of pregnancy. The decrease in glycodelin inthe endometrium is associated with glandular regression duringthe first third of pregnancy. In contrast, IGFBP-1 is only observedin the deep basal glands during the luteal phase. Followingthe establishment of pregnancy, IGFBP-1 synthesis switches fromglandular to stromal and is correlated with the process of decidualization.IGFBP-1 synthesis continues to increase throughout gestation.We propose that glycodelin may have immunosuppressive propertiesand that IGFBP-1 may regulate trophoblast migration within theuterine endometrium. 相似文献
205.
Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy 总被引:4,自引:6,他引:4
McNally EM; Duggan D; Gorospe JR; Bonnemann CG; Fanin M; Pegoraro E; Lidov HG; Noguchi S; Ozawa E; Finkel RS; Cruse RP; Angelini C; Kunkel LM; Hoffman EP 《Human molecular genetics》1996,5(11):1841-1847
Recently, mutations in the genes encoding several of the dystrophin-
associated proteins have been identified that produce phenotypes ranging
from severe Duchenne-like autosomal recessive muscular dystrophy to the
milder limb-girdle muscular dystrophies (LGMDs). LGMD type 2C is generally
associated with a more severe clinical course and is prevalent in northern
Africa. A previous study identified a single base pair deletion in the gene
encoding the dystrophin-associated protein gamma-sarcoglycan in a number of
Tunisian muscular dystrophy patients. To investigate whether
gamma-sarcoglycan gene mutations cause autosomal recessive muscular
dystrophy in other populations, we studied 50 muscular dystrophy patients
from the United States and Italy. The muscle biopsies from these 50
patients showed no abnormality of dystrophin but did show diminished
immunostaining for the dystrophin- associated protein alpha-sarcoglycan.
Four patients with a severe muscular dystrophy phenotype were identified
with homozygous, frameshifting mutations in gamma-sarcoglycan. Two of the
four have microdeletions that disrupt the distal carboxyl-terminus of
gamma- sarcoglycan yet result in a complete absence of gamma-and beta-
sarcoglycan suggesting the importance of this region for stability of the
sarcoglycan complex. This region of gamma-sarcoglycan, like beta-
sarcoglycan, has a number of cysteine residues similar to those in
epidermal growth factor cysteine-rich regions.
相似文献
206.
Preparation of IgA-deficient platelets 总被引:1,自引:0,他引:1
The IgA-deficient patient presents a difficult transfusion problem, particularly if he or she has previously been immunized and has formed IgA antibodies. Blood components from IgA-deficient donors may be used safely but are often not accessible to transfusion facilities. A satisfactory red cell component may be obtained by standard freezing and washing methods. There is no comparable platelet concentrate that uniformly affords protection against anti-IgA-mediated reactions. A method has been developed for the preparation of an IgA-deficient platelet concentrate by washing with citrate-buffered saline. Platelets prepared in this manner were transfused successfully to an IgA-deficient patient with a history of anaphylaxis related to transfusion. It was further demonstrated that the removal of IgA is enhanced if platelets are washed within 48 hours of collection. When platelets were stored for more than 48 hours, similar washing techniques resulted in significantly higher levels of IgA in the platelets washed with either buffered (p = 0.004) or unbuffered (p = 0.0002) saline. Platelets washed with unbuffered saline (pH 4.5-5.5) contained substantially more IgA than did platelets washed in a similar manner with citrate-buffered saline (pH 6.5-6.8) (p = 0.001). 相似文献
207.
208.
Annette Kurre Caroline HG Bastiaenen Christel JAW van Gool Thomas Gloor-Juzi Eling D de Bruin Dominik Straumann 《BMC ear, nose, and throat disorders》2010,10(1):1-10
Background
The Dizziness Handicap Inventory (DHI) is a validated, self-report questionnaire which is widely used as an outcome measure. Previous studies supported the multidimensionality of the DHI, but not the original subscale structure. The objectives of this survey were to explore the dimensions of the Dizziness Handicap Inventory - German version, and to investigate the associations of the retained factors with items assessing functional disability and the Hospital Anxiety and Depression Scale (HADS). Secondly we aimed to explore the retained factors according to the International Classification of Functioning, Disability and Health (ICF).Methods
Patients were recruited from a tertiary centre for vertigo, dizziness or balance disorders. They filled in two questionnaires: (1) The DHI assesses precipitating physical factors associated with dizziness/unsteadiness and functional/emotional consequences of symptoms. (2) The HADS assesses non-somatic symptoms of anxiety and depression. In addition, patients answered the third question of the University of California Los Angeles-Dizziness Questionnaire which covers the impact of dizziness and unsteadiness on everyday activities. Principal component analysis (PCA) was performed to explore the dimensions of the DHI. Associations were estimated by Spearman correlation coefficients.Results
One hundred ninety-four patients with dizziness or unsteadiness associated with a vestibular disorder, mean age (standard deviation) of 50.6 (13.6) years, participated. Based on eigenvalues greater one respectively the scree plot we analysed diverse factor solutions. The 3-factor solution seems to be reliable, clinically relevant and can partly be explained with the ICF. It explains 49.2% of the variance. Factor 1 comprises the effect of dizziness and unsteadiness on emotion and participation, factor 2 informs about specific activities or effort provoking dizziness and unsteadiness, and factor 3 focuses on self-perceived walking ability in relation to contextual factors. The first factor correlates moderately with disability and the HADS (values ≥0.6). The second factor is comparable with the original physical subscale of the DHI and factors retained in previous studies.Conclusions
The results of the present survey can not support the original subscale structure of the DHI. Therefore only the total scale should be used. We discuss a possible restructuring of the DHI. 相似文献209.
210.
Cold agglutinins are a potential danger to patients who must be subjected to hypothermia. A patient with a cold agglutinin of moderate titer but broad thermal amplitude was to undergo hypothermia during aortic valve replacement. He was managed preoperatively with an eight- liter plasma exchange by continuous-flow centrifugation to remove the cold agglutinin. There were no adverse effects during or after hypothermia. 相似文献