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排序方式: 共有603条查询结果,搜索用时 15 毫秒
91.
92.
Robertson RT; Gallardo KA; Claytor KJ; Ha DH; Ku KH; Yu BP; Lauterborn JC; Wiley RG; Yu J; Gall CM; Leslie FM 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(2):142-155
The role of basal forebrain-derived cholinergic afferents in the
development of neocortex was studied in postnatal rats. Newborn rat pups
received intraventricular injections of 192 IgG-saporin. Following survival
periods ranging from 2 days to 6 months, the brains were processed to
document the cholinergic lesion and to examine morphological consequences.
Immunocytochemistry for choline acetyltransferase (ChAT) and in situ
hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the
cholinergic neurons in the medial septum and nucleus of the diagonal band
of Broca in the basal forebrain. In situ hybridization for glutamic acid
decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons.
Acetylcholinesterase histochemistry demonstrates a marked reduction of the
cholinergic axons in neocortex. Cholinergic axons are reduced throughout
the cortical layers; this reduction is more marked in medial than in
lateral cortical areas. The thickness of neocortex is reduced by
approximately 10%. Retrograde labeling of layer V cortico-collicular
pyramidal cells reveals a reduction in cell body size and also a reduction
in numbers of branches of apical dendrites. Spine densities on apical
dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated
cases; no change was detected in number of spines on basal dendrites. These
results indicate a developmental or maintenance role for cholinergic
afferents to cerebral cortical neurons.
相似文献
93.
Trimetrexate (TMTX) is an anticancer drug with potential advantages over the more commonly used antifolate, methotrexate (MTX); however, its use has been limited by severe myelosuppression. Retroviral vectors containing mutant dihydrofolate reductase (DHFR) genes have been used to protect bone marrow cells from MTX, suggesting a similar approach could be used for TMTX. We first screened six variants of human DHFR to determine which allowed maximal TMTX resistance in fibroblasts. A variant enzyme containing a Leu-to-Tyr mutation in the 22nd codon (L22Y) was best, allowing a 100-fold increase in resistance over controls. Murine hematopoietic progenitor cells transduced with an L22Y- containing retroviral vector also showed high-level TMTX resistance in vitro. Mice reconstituted with L22Y-transduced bone marrow cells were challenged with a 5-day course of TMTX to determine whether hematopoiesis could be protected in vivo. Transfer of the L22Y vector resulted in consistent protection from TMTX-induced neutropenia and reticulocytopenia at levels that correlated with the proviral copy number in circulating leukocytes. We conclude that the L22Y vector is highly effective in protecting hematopoiesis from TMTX toxicity and may provide a means for increasing the therapeutic utility of TMTX in certain cancers. 相似文献
94.
de Voogd S Wolfs RC Jansonius NM Witteman JC Hofman A de Jong PT 《Investigative ophthalmology & visual science》2006,47(9):3772-3776
PURPOSE: To test the hypotheses that atherosclerosis and elevated serum C-reactive protein (CRP) levels are risk factors for open-angle glaucoma (OAG). METHODS: In a prospective, population-based cohort study, all participants 55 years and older and at risk for incident OAG underwent, at baseline (1990-1993) and at follow-up (1997-1999), the same ophthalmic examination, including visual field testing and optic disc photography. Baseline atherosclerosis was assessed by means of echography of the carotid arteries, abdominal x-ray examination, and ankle-arm index; baseline serum CRP levels were used in the analyses. The diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Odds ratios of OAG were computed with logistic regression analyses. Risk factors were categorized in tertiles and according to standard deviation. RESULTS: After a mean follow-up of 6.5 years, incident OAG was diagnosed in 87 of 3842 (2.3%) participants at risk for OAG. Carotid artery plaques, carotid intima-media thickness, aortic calcifications, ankle-arm index, and CRP levels were not significant risk factors for OAG. The odds ratio, given for the highest and lowest tertiles, for carotid plaques was 1.43 (95% confidence interval [CI], 0.68-2.99), for carotid intima-media thickness 0.86 (95% CI, 0.47-1.57), for aortic calcifications 1.02 (95% CI, 0.60-1.75), for ankle-arm index 0.69 (95% CI, 0.38-1.25), and for CRP 1.19 (95% CI, 0.68-2.07). CONCLUSIONS: In this prospective, population-based study, neither atherosclerosis nor serum CRP level was an important risk factor for OAG. 相似文献
95.
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97.
Mattace-Raso FU van der Cammen TJ Knetsch AM van den Meiracker AH Schalekamp MA Hofman A Witteman JC 《Journal of hypertension》2006,24(2):339-344
OBJECTIVE: To investigate whether arterial stiffening, one of the characteristics of the aging vascular system, is associated with orthostatic hypotension. DESIGN: Cross-sectional data of a cohort study in elderly men and women. PARTICIPANTS: We investigated the relationship between arterial stiffness and orthostatic hypotension within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3362 subjects participating in the third examination phase. The carotid-femoral pulse wave velocity was used as measure of arterial stiffness. Orthostatic hypotension was assessed with blood pressure measurements in supine and standing position. RESULTS: Odds ratios for orthostatic hypotension increased through quartiles of pulse wave velocity; the age, gender and mean arterial pressure adjusted odds ratio in the last quartile of pulse wave velocity was 1.45 (95% confidence interval, 1.09-1.93) when compared with the first quartile (reference). In fully adjusted models estimates remained statistically significant. In subjects with higher stiffness we observed a higher drop in blood pressure but no significant change of heart rate. CONCLUSIONS: Arterial stiffness is independently associated with orthostatic hypotension. The drop in blood pressure levels and the contemporary attenuated response of heart rate to orthostatic challenge in subjects with stiffer arteries support the hypothesis that arterial stiffness may explain, at least in part, the reduced baroreflex observed in older adults. 相似文献
98.
99.
Alina Vrieling Dorien W. Voskuil Astrid Bosma Donné M. Majoor Jaap van Doorn Annemieke Cats Annekatrien C.T.M. Depla Robin Timmer Ben J.M. Witteman Jelle Wesseling Ellen Kampman Laura J. Van’t Veer 《Growth hormone & IGF research》2009,19(2):126-135
ContextThe insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are correlated.ObjectiveThe objective of this study was to determine expression levels of various IGF-system components in different locations of the colorectum, and to investigate whether normal tissue IGF expression levels are correlated with serum IGF-I and IGF-II concentrations.DesignBiopsies from macroscopically normal mucosa at four locations in the colorectum (ascending, transverse, sigmoid colon, and rectum) and a fasting serum sample were obtained from 48 asymptomatic patients at increased risk of colorectal cancer. Expression levels of IGF-I, IGF-II, IGF-IR, IGF-IIR, and IGFBP-3 messenger RNA (mRNA) in tissue were quantitatively evaluated using real-time RT-PCR. Expression of IGF-IR protein in the ascending colon and rectum tissue specimens was assessed semi-quantitatively by immunohistochemistry. Serum IGF-I and IGF-II concentrations were determined using immunometric assays.ResultsWith the exception of IGF-IIR, mRNA levels of all the IGF-system components investigated, as well as IGF-IR protein expression, were significantly higher in the rectum compared with the ascending colon (p ? 0.001). Serum IGF-I and IGF-II concentrations did not correlate with any of the parameters studied in colorectal tissues.ConclusionsOur results indicate that in humans IGF-system components are differentially expressed in the colorectum. Moreover, our findings suggest that local and circulating components of the IGF-system are differentially regulated. However, due to large intra-individual variation in mRNA expression, we cannot formally exclude undetected but existing routes of co-regulation. 相似文献
100.