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251.
FN Engsig LH Omland MV Larsen LD Rasmussen T Qvist J Gerstoft N Obel 《HIV medicine》2010,11(7):457-461
Objectives
According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.Methods
A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.Results
We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.Conclusion
The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low. 相似文献252.
Zimmermann RC; Krahn L; Rahmanie N; Sauer MV 《Human reproduction (Oxford, England)》1998,13(4):822-825
Leptin has been called a hormone of reproduction, and seems to link fat and
fertility. It has been speculated that the neurotransmitter norepinephrine
(NE) (noradrenaline), possibly via the sympathetic nervous system, may
represent the afferent signal which modulates leptin release from
adipocytes. The purpose of this study was to produce a state of decreased
sympathetic output by using the catecholamine synthesis inhibitor
alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this
compound on the secretion of leptin from fat cells. Ten subjects (five
women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg
promethazine (active placebo) over a 26 h period, separated by 4-6 weeks
using a randomized, double- blind, placebo-controlled, cross-over design.
Blood samples for hormone measurements were obtained over 24 h (18 time
points) on day 2 of each experiment. Urinary measurement of the NE
metabolite 3-methoxy-4- hydroxyphenylglycol (MHPG) on study day 2 served as
a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The
daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the
placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P <
0.05). Plasma leptin concentrations measured in the control group in women
and men were similar to those reported previously in lean subjects with a
body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold
higher than in men. Leptin is secreted in a circadian rhythm in both sexes
with an increase of nocturnal concentrations by approximately 50%. Two-way
analysis of variance reveals no significant difference in leptin secretion
between the control and active groups in women and men. In summary,
preliminary results do not support the hypothesis that NE represents the
afferent signal from the central nervous system which modulates leptin
release from adipocytes in the human. Further studies are needed to define
the role of the sympathetic nervous system as well as NE in the regulation
of leptin secretion and its involvement in obesity and reproduction.
相似文献
253.
254.
255.
The spontaneous disappearance of the inhibitor to factor VIII (FVIII) was observed in two human immunodeficiency virus (HIV)-infected men with hemophilia A. Both men had end-stage HIV infection, one with acquired immune deficiency syndrome (AIDS) and one with severe AIDS-related complex (ARC). Loss of the inhibitor was associated with a fall in T4 helper lymphocytes to less than 100 per mm3 in both patients. Subsequent spontaneous and traumatic hemorrhages were treated successfully with standard doses of FVIII concentrate, resulting in adequate FVIII:C levels and good hemostasis. The mechanism by which the anti-FVIII inhibitor disappears is not known, but it is likely to be related to a quantitative decline in T4 cell number. 相似文献
256.
Cell-lineage antigens of the stem cell-megakaryocyte-platelet lineage are associated with the platelet IIb-IIIa glycoprotein complex 总被引:5,自引:2,他引:3
The stem cell-platelet lineage is uniquely defined by platelet cell- lineage antigens. These antigens are present on all stem cells measured by the spleen colony assay and become restricted to the platelet cell lineage as differentiation proceeds. In this study, anti-platelet serum (APS) has been used to identify cells in the bone marrow that express platelet cell-lineage antigens and to identify platelet cell surface molecules expressing these antigens. Anti-platelet IgG extensively absorbed with brain, thymus, and peritoneal cells bound selectively to stem cells, megakaryocyte progenitor cells (Mk-CFC), and megakaryocytes in CBA mouse bone marrow and to blood platelets. No other hemopoietic cell type, tissue, cell line, or tumor cell bound significant amounts of antibody against platelet cell-lineage antigens as determined by ability to absorb the anti-stem cell activity in APS. Studies with lactoperoxidase-labeled platelets showed that two major iodinated proteins of Mr = 114,000 and 138,000 were immunoprecipitated with APS and with antiserum that had been extensively absorbed. These proteins correspond to the platelet IIb-IIIa glycoprotein complex, which is known to express receptors for collagen and fibrinogen, molecules known to influence hemopoietic cell proliferation and tumor cell growth. A panel of six monoclonal antibodies against human IIb-IIIa inhibited spleen colony formation by 17% to 100%, J15 and A5.15 also being cytotoxic for granulocyte-macrophage progenitor cells and Mk-CFC. Other platelet monoclonal antibodies did not inhibit spleen colony formation. Although APS inhibited fibrinogen binding to platelets and platelet aggregation, these activities were greatly reduced with absorbed antiserum. Furthermore, fibrinogen treatment of bone marrow did not block the anti-stem cell activity in APS. Thus the evidence is consistent with expression of platelet cell-lineage antigens on the platelet IIb-IIIa glycoprotein complex at a site removed from the fibrinogen binding site. 相似文献
257.
Metabolic activation of aromatic amines by human pancreas 总被引:4,自引:3,他引:4
Anderson KE; Hammons GJ; Kadlubar FF; Potter JD; Kaderlik KR; Ilett KF; Minchin RF; Teitel CH; Chou HC; Martin MV; Guengerich FP; Barone GW; Lang NP; Peterson LA 《Carcinogenesis》1997,18(5):1085-1092
Epidemiologic studies have suggested that aromatic amines (and
nitroaromatic hydrocarbons) may be carcinogenic for human pancreas.
Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were
examined for their ability to metabolize aromatic amines and other
carcinogens. Microsomes showed no activity for cytochrome P450 (P450)
1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following
activities (and associated P450s): aminopyrine N-demethylation and
ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O- deethylation
(P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol
hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1);
lauric acid omega-hydroxylation (P450 4A1); and 4-
(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450
1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450
1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase.
Immunoblots detected only epoxide hydrolase at low levels; P450 levels were
<1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation
activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl
reductase activities were present at levels comparable to human liver. The
O-acetyltransferase activity (AcCoA- dependent DNA-binding of
[3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the
levels measured in human colon. Cytosols showed high activity for
N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating
that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue.
Cytosolic sulfotransferase was detected at low levels. Using
32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA
adducts were detected in most samples. Moreover, in eight of 29 DNA
samples, a major adduct was observed that was chromatographically identical
to the predominant ABP- DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These
results are consistent with a hypothesis that aromatic amines and
nitroaromatic hydrocarbons may be involved in the etiology of human
pancreatic cancer.
相似文献
258.
Carmina E; Wong L; Chang L; Paulson RJ; Sauer MV; Stanczyk FZ; Lobo RA 《Human reproduction (Oxford, England)》1997,12(5):905-909
Polycystic-appearing ovaries (PAO) on ultrasound have been described in a
variety of endocrinopathies and also occur in ovulatory women. By some
investigators this is merely referred to as 'PCO' (polycystic ovaries).
Although there is controversy in this regard, we do not consider women with
PAO/PCO who have no known endocrine disturbance to have polycystic ovary
syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is
often equated with PCOS. We studied 15 ovulatory women with
normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women
with PAO/PCO. Compared to ovulatory women, 25 other women were studied who
were considered to have PCOS. Of these, 15 were overweight and 10 were of
normal weight. All the PCOS women had serum concentrations of luteinizing
hormone (LH), testosterone, unbound testosterone, androstenedione and
dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P
< 0.01) than values in the normal women, regardless of ovarian
morphology. These values were similar in the two groups of ovulatory women
with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with
increased body weight (P < 0.01) and was higher than in ovulatory women
with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum
insulin- like growth factor (IGF)-I and binding protein (BP)-3 were similar
in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in
those women with PCOS with increased body weight, compared to all other
groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was
also significantly (P < 0.05) lower in women with PAO/PCO and those
women with PCOS of normal weight. These lower values were similar in women
with PAO/PCO and in normal weight women with PCOS. On an individual basis,
an elevation of at least one serum androgen value was found in 33% of women
with PAO/PCO. These data confirm that increased body weight accentuates the
metabolic alterations in PCOS, but suggest that subtle endocrine
disturbances, similar to those that are found in PCOS, may be uncovered in
up to a third of ovulatory women with PAO/PCO. It appears that a
disturbance of the IGF/IGFBP-1 axis is common and apparently closely
associated with alterations in ovarian morphology.
相似文献
259.
260.
JP Zappulla L Wickham W Bawab XF Yang MV Storozhuk VF Castellucci L DesGroseillers 《The Journal of neuroscience》1999,19(11):4280-4292
Cell surface metallo-endopeptidases play important roles in cell communication by controlling the levels of bioactive peptides around peptide receptors. To understand the relative relevance of these enzymes in the CNS, we characterized a metallo-endopeptidase in the CNS of Aplysia californica, whose peptidergic pathways are well described at the molecular, cellular, and physiological levels. The membrane-bound activity cleaved Leu-enkephalin at the Gly3-Phe4 bond with an inhibitor profile similar to that of the mammalian neutral endopeptidase (NEP). This functional homology was supported by the molecular cloning of cDNAs from the CNS, which demonstrated that the Aplysia and mammalian NEPs share all the same amino acids that are essential for the enzymatic activity. The protein is recognized both by specific anti-Aplysia NEP (apNEP) antibodies and by the [125I]-labeled NEP-specific inhibitor RB104, demonstrating that the apNEP gene codes for the RB104-binding protein. In situ hybridization experiments on sections of the ganglia of the CNS revealed that apNEP is expressed in neurons and that the mRNA is present both in the cell bodies and in neurites that travel along the neuropil and peripheral nerves. When incubated in the presence of a specific NEP inhibitor, many neurons of the buccal ganglion showed a greatly prolonged physiological response to stimulation, suggesting that NEP-like metallo-endopeptidases may play a critical role in the regulation of the feeding behavior in Aplysia. One of the putative targets of apNEP in this behavior is the small cardioactive peptide, as suggested by RP-HPLC experiments. More generally, the presence of apNEP in the CNS and periphery may indicate that it could play a major role in the modulation of synaptic transmission in Aplysia and in the metabolism of neuropeptides close to their point of release. 相似文献