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排序方式: 共有348条查询结果,搜索用时 78 毫秒
91.
Down-regulation of survivin expression in T lymphocytes after interferon beta-1a treatment in patients with multiple sclerosis 总被引:3,自引:0,他引:3
BACKGROUND: Treatment with interferon beta reduces clinical exacerbations in multiple sclerosis (MS) through several immunomodulatory mechanisms that involve the augmentation of programmed cell death (apoptosis) of peripheral T lymphocytes. The expression of survivin, a cell cycle-regulated antiapoptosis protein, is up-regulated in mitogen-stimulated T lymphocytes from patients with MS, and this expression correlates with MS disease activity. OBJECTIVE: To evaluate the effect of interferon beta on the expression of survivin and other apoptosis regulatory molecules in peripheral T lymphocytes from patients with MS. PATIENTS AND METHODS: In a prospective, combined clinical and immunologic study, we evaluated the expression of survivin, Bcl-2 protein, and the death receptor Fas in mitogen-stimulated T lymphocytes from 26 patients with MS, before and serially after treatment with interferon beta-1a. We also investigated the long-term effects of interferon beta-1a on cellular expression of these proteins and T-lymphocyte apoptosis in a cross-sectional study of 19 patients with MS receiving long-term interferon beta-1a therapy. RESULTS: Treatment with interferon beta-1a reduced the expression of survivin in in vitro stimulated T lymphocytes. This reduced expression correlated with augmented T-cell susceptibility to apoptosis and with clinical response to treatment. In contrast, interferon beta-1a therapy did not significantly alter cellular expression of Bcl-2 protein or Fas. This down-regulatory effect of interferon beta-1a on cellular expression of survivin was maintained after long-term therapy. CONCLUSIONS: Our observations suggest that interferon beta exerts a regulatory effect on peripheral T lymphocytes through an antiapoptosis mechanism that involves the down-regulation of cellular survivin expression. 相似文献
92.
93.
Bioactivation of the mushroom hydrazine, agaritine, to intermediates that bind covalently to proteins and induce mutations in the Ames test 总被引:1,自引:0,他引:1
The present study was undertaken to establish whether liver and kidney
enzyme systems, from rat and mouse, have the potential to metabolise and
bioactivate agaritine, beta-N-(gamma-L(+)glutamyl)-4-
(hydroxymethyl)phenylhydrazine, the most abundant hydrazine present in the
edible mushroom Agaricus bisporus. Agaritine was weakly mutagenic, in the
absence of an activation system, in Salmonella typhimurium strain TA104.
Rat kidney homogenates, characterised by high gamma- glutamyl
transpeptidase activity, enhanced the mutagenic response. In contrast,
hepatic microsomes, having very low gamma-glutamyl transpeptidase activity,
did not influence the mutagenicity of agaritine. However, hepatic
microsomes could further potentiate the mutagenic response induced by the
kidney. Agaritine was a good substrate for purified gamma-glutamyl
transpeptidase, being converted to a major metabolite,
4-(hydroxymethyl)phenylhydrazine, formed as a result of the loss of the
glutamyl moiety. Kidney homogenates from the rat and mouse also catalysed
this reaction, the former being the more effective. Metabolism of agaritine
was suppressed by serine-borate, an inhibitor of gamma-glutamyl
transpeptidase. Kidney homogenates from rat and mouse could metabolise
agaritine to intermediate(s) that bound covalently to proteins, with the
rat preparations being the more effective; covalent binding was inhibited
by glutathione. In contrast, hepatic preparations alone were ineffective in
producing such covalent binding but did further increase the covalent
binding mediated by the kidney preparations. It is concluded that rat and
mouse kidney homogenates catalyse the removal of the glutamyl group from
agaritine to yield the reactive free hydrazine, which is further converted
to the highly reactive diazonium ion by hepatic microsomes.
相似文献
94.
Yen CC; Hsieh RK; Chiou TJ; Liu JH; Fang FS; Wang WS; Tung SL; Tzeng CH; Chen PM 《Japanese journal of clinical oncology》1998,28(2):129-133
The anti-emetic efficacy of a combination of tropisetron and dexamethasone
was studied in 33 patients who underwent bone marrow transplantation.
Another 50 patients receiving conventional anti-emetic therapies in bone
marrow transplantation served as control. On the first and second days of
preconditioning chemotherapy, 51% and 36% respectively of patients in the
tropisetron and dexamethasone group did not experience vomiting, compared
with only 12% and 10% of control group patients (P < 0.001). The mean
number of episodes of vomiting in the tropisetron and dexamethasone group
was also significantly lower than in the control group (0.97+/-1.65 vs
3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P <
0.001). Control of vomiting in the two groups was not significantly
different during days 3-6. Analysis of patients receiving busulfan and
cyclophosphamide as the preconditioning regimen still showed better
anti-emetic control in the tropisetron and dexamethasone group than in the
control group on the first two days of treatment (total control rate 33.3%
vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given
tropisetron and dexamethasone combination more frequently suffered from
dizziness and burning sensation of the chest. However, diarrhea and
extrapyramidal symptoms were the most frequent adverse effects seen after
using conventional anti-emetic combination. The combination of tropisetron
and dexamethasone was thus superior to conventional anti-emetic
combinations in preventing vomiting during preconditioning period of bone
marrow transplantation. The adverse effects of this combination were
minimal and well tolerated by patients.
相似文献
95.
Chiou TJ; Tung SL; Hsieh RK; Wang WS; Yen CC; Fan FS; Liu JH; Chen PM 《Japanese journal of clinical oncology》1998,28(5):318-322
BACKGROUND: The efficacy of the treatment of advanced gastric cancer is not
very good. The response rate to the original
etoposide--leucovorin--5-fluorouracil (ELF) treatment is 53% with tolerable
side effects. Whether increasing the dose intensity by prolonging the
duration of infusion with 5-fluorouracil (5-FU) and leucovorin (LV) from 3
to 5 days for advanced or metastatic gastric cancer patients would enhance
the efficacy but not increase side effects is still unknown. METHODS:
Thirty-six advanced or metastatic gastric cancer and chemotherapy-naive
patients with measurable or evaluable diseases were scheduled to receive
intravenous etoposide 100 mg/m2/day on days 2-4, LV 300 mg/m2/day
intravenously and 5-FU 500 mg/m2/day intravenously on days 1-5, every 4
weeks. All patients who received at least two courses of chemotherapy were
evaluated for tumor response, survival and response duration and toxicity
according to the WHO criteria. RESULTS: Thirteen patients showed a
response, including five with complete response (CR). The overall response
rate was 36% (95% confidence interval, CI, 20-52%) in the whole group and
46% (95% CI 28-66%) in the 28 patients with measurable disease. The median
progression-free interval and overall median survival time were 5 and 7
months, respectively. The most frequent toxicity was alopecia (grade I/II
56.3%). The incidence of grade III or greater myelosuppression was 5.9%. No
treatment-related death occurred. CONCLUSIONS: The efficacy of the modified
ELF by increasing the dosages of 5-FU and LV is not superior to the results
of the original regimen, yet it is a relatively safe and tolerable
combination regimen for advanced gastric cancer.
相似文献
96.
Human sperm non-nuclear progesterone receptor expression is a novel marker for fertilization outcome 总被引:1,自引:0,他引:1
Jacob A; Hurley I; Mandel FS; Hershlag A; Cooper GW; Benoff S 《Molecular human reproduction》1998,4(6):533-542
In a prospective, blind study, we have examined the relationship among the
expression of human sperm surface progesterone receptors, the ability to
undergo a mannose-stimulated acrosome reaction and the rate of
fertilization in vitro. Individual aliquots of motile spermatozoa were
surface-labelled with progesterone and/or mannose-fluoresceinated ligands.
Spontaneous acrosome loss and the increase in acrosome reactions following
exposure of spermatozoa to mannose ligands were assessed using rhodaminated
Pisum sativum agglutinin. Progesterone fluoresceinated ligand binding was
observed to occur in two patterns: (i) a uniform distribution of labelling
over the acrosome cap (pattern II), and (ii) labelling limited to the
equatorial and postacrosomal regions of the human sperm head (pattern III).
A conversion of pattern II to pattern III binding was observed and was
associated with the acrosome reaction. Pattern III binding was highly
correlated with both fertilization potential and the ability to undergo a
mannose-stimulated acrosome reaction (P < 0.001). In contrast, normal
sperm mannose receptor expression was seen in five men whose abnormal
progesterone receptor expression/function and inability to acrosome react
after mannose treatment were correlated with their reduced fertility in
vitro. In conclusion, surface progesterone receptor aggregation enhances
the mannose ligand-stimulated acrosome reaction. Such detection of
defective sperm surface progesterone receptor expression/function may be
useful in the evaluation and management of male infertility.
相似文献
97.
Sameena Wazir Saheed Shittu Khaled Dukhan Maram Sharief Stephen Beer Waseem Malik Lolwa Alansari 《Clinical Case Reports》2022,10(4)
Diabetic ketoacidosis (DKA) is a life‐threatening complication of diabetes and is considered a medical emergency. Euglycemic DKA (EKDA) is a variant of DKA with a normal or minimally elevated glucose level <200 mg/dl. The condition can be difficult to diagnose due to the relatively normal glucose levels. Pregnancy, infection, and a low‐calorie intake are some of the contributing common etiologies of EDKA. Despite a rapid increase in scientific publications on COVID‐19, there are still knowledge gaps regarding the course of COVID‐19 in some patient subset. This is especially the case for pregnant women. In this case report, we discuss the course of COVID‐19 infection in a pregnant woman with gestational diabetes who developed severe euglycemic diabetic ketoacidosis triggered by various precipitating factors, including starvation, caused by COVID‐19 infection and its gastrointestinal effects. 相似文献
98.
A 36-year-old dental technician for 14 years developed paraesthesia and numbness in her legs. Neurophysiological studies revealed absent sensory nerve action potentials (SNAPs) from her lower limbs and normal upper limb SNAPs on presentation. Motor nerve studies were normal. Repeat studies 2 months after leaving her job showed some improvement in the lower limb SNAPs. It is suggested that her symptoms were caused by occupational exposure to methyl methacrylate monomer. 相似文献
99.
Andreas Wellmer Vijay Peter Misra Mohammad K. Sharief Peter G. Kopelman Praveen Anand 《Journal of the peripheral nervous system : JPNS》2001,6(4):204-210
A randomized, double-blind, placebo-controlled study of brain-derived neurotrophic factor (rhBDNF) was conducted in 30 patients with insulin-treated diabetes mellitus, with obligatory abnormalities of sural nerve conduction studies and vibration perception threshold (VPT) at the great toe on recruitment. Nine patients received placebo, 11 rhBDNF (25 microg/ kg) and 10 rhBDNF (100 microg/kg) s.c. daily for 3 months, and were assessed at days 0, 8, 15, 29, 43, 57 and 85 with nerve conduction and quantitative sensory and autonomic tests including VPT, thermal and light touch thresholds, and cutaneous axon-reflexes. No statistically significant differences were found among the 3 treatment groups between baseline and day 85 values. To examine possible reasons for lack of effect, post hoc analysis was performed. In the subset of patients with abnormal but detectable cool detection threshold (CDT) at baseline, there was improvement of CDT at day 85 when compared to baseline in the treated (p < 0.02) but not placebo group. Further, from days 43 to 85, in the treated group but not the placebo group, CDT was indistinguishable from a group of matched normal subjects (p > 0.05). Skin biopsies failed to show evidence of structural change; assessment of innervation of hair follicles, which is partly dependent on BDNF, was not possible because of the marked loss of this end-organ in diabetic neuropathic skin. The only side effects of rhBDNF were infrequent non-painful injection-site skin reactions and increased gut motility at the higher dose. We conclude that further preclinical studies are warranted before any future clinical trials to see if rhBDNF improves CDT and constipation in diabetics. 相似文献
100.
Saccadic strategies in children with hemianopia 总被引:1,自引:1,他引:0
LE Mezey BSc C M Harris PhD FS Shawkat PhD C. Timms DBO A. Kriss PhD P. West D S I Taylor FRCS FRCOphth 《Developmental medicine and child neurology》1998,40(9):626-630
Multiple hypometric (undershooting) saccades are generally reported as a compensatory strategy in adults with homonymous hemianopia. However, hypermetric (overshooting) saccades have been reported to develop spontaneously as a beneficial strategy in response to predictable targets. We examined the saccades of 10 children (aged 5 to 16 years) with homonymous hemianopia to determine the type of compensatory eye-movement strategies employed 6 months to 16 years after hemianopia onset. Homonymous hemianopia was identified using perimetry and/or pattern visual evoked potentials and supported with results of neuroimaging. Eye movements were recorded using bitemporal electrooculography. Saccades were elicited to a red light source in a semipredictable paradigm. We found that hypermetria was not a consistent compensatory strategy in our patients. In spite of the predictability of our paradigm and the long follow-up period, multiple hypometric saccades into the blind field appeared to be the preferred strategy. 相似文献