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11.
A study of the degree of progesterone support required for the maintenance
of various stages of pregnancy was undertaken in mice. Mated females were
ovariectomized at various stages of pregnancy and progesterone and
oestradiol support provided by s.c. Silastic implants with known release
characteristics. In the earliest stages of pregnancy (days 1-5), very low
concentrations of progesterone (<25% of normal physiological values)
were sufficient to maintain pre-implantation stages and allow implantation.
In the immediate post-implantation period (days 5-9), the development of
implantation sites and decidualization required considerably higher
progesterone support. In mid-pregnancy (days 11-14), progesterone alone
could not maintain pregnancy unless present in very high amounts; however,
the presence of oestradiol during this period lowered the progesterone
requirements to well within the physiological range. This effect of
oestradiol started on day 11 but required the level of oestradiol support
to be kept within strictly defined limits, with high concentrations
inducing abortion. Progesterone alone was able to maintain pregnancy from
day 15. These results indicate that the minimal progesterone support
required for pregnancy in mice varies considerably at different stages of
pregnancy and is at least partly modulated by oestradiol.
相似文献
12.
Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome 总被引:3,自引:4,他引:3
Sirotkin H; Morrow B; DasGupta R; Goldberg R; Patanjali SR; Shi G; Cannizzaro L; Shprintzen R; Weissman SM; Kucherlapati R 《Human molecular genetics》1996,5(5):617-624
Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are
developmental disorders characterized by a spectrum of phenotypes including
velopharyngeal insufficiency, conotruncal heart defects and facial
dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS
patients are hemizygous for a portion of chromosome 22. It is likely that
the genes encoded by this region play a role in the etiology of the
phenotypes associated with the disorders. Using a cDNA selection protocol,
we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS
minimally deleted interval. The cDNA encodes a protein of 1638 amino acids.
CLTD shares significant homology, but is not identical to the ubiquitously
expressed clathrin heavy chain gene. The CLTD gene also shows a unique
pattern of expression, having its maximal level of expression in skeletal
muscle. Velopharyngeal insufficiency and muscle weakness are common
features of VCFS patients. Based on the location and expression pattern of
CLTD, we suggest hemizygosity at this locus may play a role in the etiology
of one of the VCFS-associated phenotypes.
相似文献
13.
Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose 总被引:16,自引:0,他引:16
Craft S Asthana S Newcomer JW Wilkinson CW Matos IT Baker LD Cherrier M Lofgreen C Latendresse S Petrova A Plymate S Raskind M Grimwood K Veith RC 《Archives of general psychiatry》1999,56(12):1135-1140
BACKGROUND: Increasing plasma glucose levels improves memory in patients with Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improvement is due to changes in insulin, independent of hyperglycemia. We address this question by examining memory and counterregulatory hormone response during hyperglycemia when endogenous insulin was suppressed by concomitant infusion of the somatostatin analogue octreotide (Sandostatin). METHODS: Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsulinemia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [225 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somatostatin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium chloride solution (saline) infusion (fasting insulin and glucose); and (4) an active control condition in which somatostatin alone was infused (150 mg/h). Declarative memory (story recall) and selective attention (Stroop interference test) were measured during steady metabolic states. RESULTS: Patients with AD showed improved memory during hyperinsulinemia relative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatostatin analogue infusion alone also improved memory for patients with AD (P<.05). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. CONCLUSIONS: These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD. 相似文献
14.
We report a difference in the response of serum homovanillic acid (HVA) and in the performance of some psychological tasks before and after the administration of testosterone enanthate (TE, 100 or 300 mg/wk) or nandrolone decanoate (ND, 100 or 300 mg/wk) for 6 wk to healthy men. Serum HVA was significantly increased in both the low- and high-dose ND groups, from 8.4 +/- 1.0 and 8.7 +/- 0.5 pmol/ml (mean +/- SE) to 11.6 +/- 1.7 and 10.7 +/- 1.1 pmol/ml respectively. No significant changes in HVA were observed for the groups administered TE, nor in 5-HIAA for any of the groups. The influence of ND on the dopaminergic system, which is reflected in increased serum HVA, appears to be independent from the psychological effects which were produced by both androgens. The only change in psychomotor test performance was an improvement in the first trial of a pegboard task. All subjects except those receiving ND (100 mg/wk) were significantly more optimistic in the prediction of their own performance for all nondominant hand tasks (pegboard and finger tapping). The "hostility" and "resentment and aggression" subscales of the MMPI increased significantly in all groups, more so in the high-dose groups. 相似文献
15.
The case of a 40-year-old woman with primary small cell carcinoma of the cervix is reported. She developed widespread metastates and florid Cushing's syndrome. Serum ACTH levels were greatly elevated and no site of production other than the tumor could be demonstrated at autopsy. The tumor cells demonstrated features characteristic of cells of the APUD series. Such cells have been demonstrated in normal cervical epithelium; it is likely that they may become malignant, giving rise to tumors with a potential to secrete polypeptide hormones. This case suggests that endocrine active "Apudomas" may arise from the uterine cervix. Certainly, patients with small cell carcinoma of the cervix should be investigated with appropriate serum assays for polypeptide hormones. 相似文献
16.
High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis. 总被引:1,自引:0,他引:1
The pathophysiology of the myelodysplastic syndromes (MDS) is incompletely understood. Tumor necrosis factor (TNF)alpha levels are elevated, particularly in early-stage MDS, and apoptosis in marrow cells is upregulated. Observations in other models have shown a role for insulin-like growth factor binding protein 3 (IGFBP-3) in TNFalpha-mediated apoptosis. We observed increased levels of IGFBP-3 in the marrow plasma of patients with MDS (P = 0.005) and hypothesized that altered IGFBP-3 levels contribute to the dysregulation of hemopoiesis in MDS by affecting proliferation and apoptosis. Western analysis of marrow plasma from MDS patients revealed an increase in the ratio of intact vs fragmented IGFBP-3 in early-stage MDS (relative to controls) that decreased with MDS disease progression, suggesting increased proteolysis with more advanced disease. Thus, these results provide evidence for dysregulation of IGFBP-3 in patients with MDS. While the data are complex, they are consistent with a modulatory effect of IGFBP-3 on hemopoiesis in MDS. Conceivably, understanding these mechanisms may allow for the development of novel therapeutic strategies. 相似文献
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Resistance to the latest advanced prostate cancer therapies, including abiraterone and enzalutamide, is associated with increased expression of constitutively active androgen receptor splice variants (AR-Vs). The exact mechanism by which these therapies result in AR-Vs is unknown, but may include genomic rearrangement of the androgen receptor gene as well as alternative splicing of the AR pre-messenger RNA (mRNA). An additional complication that hinders further development of effective AR strategies is that the mechanisms by which the directed therapies are bypassed may vary. Finally, the question must be addressed as to whether the androgen receptor remains to be the driver of most castration resistant disease or whether truly AR-independent tumors arise after successful androgen ablation therapy. In this review, we will examine androgen receptor splice variants as an alternative mechanism by which prostate cancer becomes resistant to androgen receptor-directed therapy. 相似文献