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71.
Evaluating the Role of Genetic Variants on first‐line antiepileptic drug response in North India: Significance of SCN1A and GABRA1 Gene Variants in Phenytoin Monotherapy and its Serum Drug Levels 下载免费PDF全文
72.
Sridar C Kent UM Notley LM Gillam EM Hollenberg PF 《The Journal of pharmacology and experimental therapeutics》2002,301(3):945-952
Tamoxifen is primarily used in the treatment of breast cancer. It has been approved as a chemopreventive agent for individuals at high risk for this disease. Tamoxifen is metabolized to a number of different products by cytochrome P450 enzymes. The effect of tamoxifen on the enzymatic activity of bacterially expressed human cytochrome CYP2B6 in a reconstituted system has been investigated. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified CYP2B6 was inactivated by tamoxifen in a time- and concentration-dependent manner. Enzymatic activity was lost only in samples that were incubated with both tamoxifen and NADPH. The inactivation was characterized by a K(I) of 0.9 microM, a k(inact) of 0.02 min(-1), and a t(1/2) of 34 min. The loss in the 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity did not result in a similar percentage loss in the reduced carbon monoxide spectrum, suggesting that the heme moiety was not the major site of modification. The activity of CYP2B6 was not recovered after removal of free tamoxifen using spin column gel filtration. The loss in activity seemed to be due to a modification of the CYP2B6 and not reductase because adding fresh reductase back to the inactivated samples did not restore enzymatic activity. A reconstituted system containing purified CYP2B6, NADPH-reductase, and NADPH-generating system was found to catalyze tamoxifen metabolism to 4-OH-tamoxifen, 4'-OH-tamoxifen, and N-desmethyl-tamoxifen as analyzed by high-performance liquid chromatography analysis. Preliminary studies showed that tamoxifen had no effect on the activities of CYP1B1 and CYP3A4, whereas CYP2D6 and CYP2C9 exhibited a 25% loss in enzymatic activity. 相似文献
73.
S Boopathy Vijayaraghavan Vaijayanthi Raja T V Chitra 《Journal of ultrasound in medicine》2003,22(7):747-752
An interrupted inferior vena cava (IVC) and a left-sided subrenal (postrenal) IVC with azygos or hemiazygos continuation are very rare anomalies of the IVC. The prenatal sonographic and color Doppler features of these anomalies are reported here. 相似文献
74.
This paper reports on a small phenomenological study that set out to describe what it means to have a child with thalassaemia regularly attending hospital for blood transfusion. Ten parents were invited to participate from the thalassaemia unit of a large hospital in a north-west province of Sri Lanka. Data were collected by in-depth interviews with parents. The participants' experiences are described as they reveal, in their own words, what it means to support children with this disease. With startling reality, this research portrays the problems associated with caring for these children and their regular admission to hospital. Three themes are used to present the participant's experience: worries, medical services, and helping and being helped. The findings of the study show that there have been improvements in the service and treatment of these children in Sri Lanka. However, the lives of the parents are still dire. This research should be useful locally in terms of increasing awareness of thalassaemia and raising the consciousness of Sri Lankan nurses and other health care workers, so that they are more aware of the parents' needs. Although phenomenological research is not generalizable, it is likely that the experience of the parents in this study has similarities throughout the developing world. 相似文献
75.
Sumitra?AroraEmail authorView authors OrcID profile Navin?Mogha Tulsi?Bhardwaj Chitra?Srivastava 《Proceedings of the National Academy of Sciences, India. Section B.》2017,87(4):1229-1236
The solvent extracts of four plants, viz. Polyalthia longifolia (Sonn.) Thw. (PL), Paederia foetida (PF), Limonia acidissima L. (LA) and Balanites aegyptiaca (L.) Del. (BA), from different families, were screened for their antifeedant, insecticidal and insect growth regulatory potential against important crop pests. The solvent extracts, namely methanol, petroleum ether, chloroform and water, of all four plants were tested for their bio-activity against lepidopteran insect pest, Spodoptera litura; and sucking insect pest, L. erysimi (mustard aphid). It was observed that Polyalthia longifolia (methanol extract) exhibited maximum potency with least concentration of 0.1 % (~1080 ppm) to give 50 % antifeedancy, followed by P. longifolia (petroleum ether) with a value of 0.2 % (~2360 ppm) and Limonia acidissima (methanol) and L. acidissima (petroleum ether). The least active compound for antifeedancy was found in the aqueous extract of Balanites aegyptica. Out of 16 plant extracts bio-assayed, methanol showed potential antifeedancy when compared with chloroform, water and petroleum ether extracts. But chloroform and petroleum ether extracts of all four plants gave very promising insecticidal activity against aphids, in comparison to other two extracts. L. acidissima (water), B. aegyptica (methanol), P. longifolia (methanol) and P. foetida (water) did not give any insecticidal activity with 50 % lethal concentration (LC50) up to 0.1 % as maximum concentration. 相似文献
76.
Von Weymarn LB Sridar C Hollenberg PF 《The Journal of pharmacology and experimental therapeutics》2004,311(1):71-79
The homologous rat cytochrome P450s 2B1 and 2B2 differ by 13 amino acids. A chimeric construct of P450 2B1/2B2 was used in conjunction with several site-directed mutants to identify key residues involved in the inactivation of P450 2B1 by two acetylenic compounds, 17alpha-ethynylestradiol (17EE) and tert-butyl 1-methyl-2-propynyl ether (tBMP). 17EE is a mechanism-based inactivator of P450 2B1 but not of P450 2B2. We show here that tBMP is also a mechanism-based inactivator of P450 2B1 and not P450 2B2. Minimal loss in 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC) activity was observed when P450 2B1 G478A was incubated with either inactivator, suggesting that this residue plays a role in the inactivation. However, P450 2B2 A478G behaved like wild-type P450 2B2, indicating that this residue alone is not sufficient for inactivation. A chimeric construct of P450 2B1/2B2 that is essentially P450 2B1 with five residues of P450 2B2 (including residue 478), was not inactivated by either tBMP or 17EE, suggesting that these five residues are important for inactivation. Sequential mutagenesis of the chimeric construct to quadruple (S407T-N417D-A419T-G478A) and triple (S407T-N417D-A419T) mutants of P450 2B1 did not result in inactivation by either inactivator. However, the triple mutant with mutations only in non-substrate recognition site (SRS) regions still exhibits wild-type P450 2B1 7-EFC O-deethylation activity with a K(m) value of 25 microM and V(max) of 8 nmol/min/nmol P450. These results demonstrate that substitution of three non-SRS residues in P450 2B1 leads to protection against inactivation of 2B enzymes by these two acetylenic compounds. 相似文献
77.
Jha P Jha P Pathak P Chosdol K Suri V Sharma MC Kumar G Singh M Mahapatra AK Sarkar C 《Experimental and molecular pathology》2011,(2):167-172
Several single nucleotide polymorphisms of the TP53 gene have been reported, amongst which polymorphism in codon 72 (rs1042522) has received significant attention and shown to be associated with disease susceptibility in different cancer types. However, there are variable reports on this polymorphism in gliomas from worldwide with inconsistent results. In addition, the implications of other polymorphic loci are not much explored in gliomas. Hence, in the present study the TP53 sequence was analyzed for all polymorphism and mutations in a total of 84 gliomas of different types and grades from patients of Indian origin. The complete sequence of all coding exons (2 to 11) and introns 2, 3, 5 and 8 of TP53 gene were studied while for introns 1, 4, 6, 7, 9 and 10, only exon flanking regions could be studied. The polymorphic loci were compared with control population. In addition to the well known codon 72 polymorphism (rs1042522), three other polymorphisms rs1642785, rs1800370 and a 16 base pair insertion in intron-3 were found. At codon 72, our study showed higher Arg/Arg genotype in gliomas compared to normal population (38% versus 13%). The Arg allele frequency in glioma patients was comparatively higher than controls (0.55 versus 0.45; P = 0.037). The Arg allele frequency was also high in adult glioblastomas compared to paediatric counterparts (0.55 versus 0.36). However, there was no significant association of TP53 mutations with any genotype of codon 72. At rs1642785, the G allele frequency was significantly higher in gliomas than in control population (0.55 versus 0.36, P = 0.005). The genotype at a 16 base pair insertion in intron-3 was almost similar in case and control. However, the polymorphism at rs1800370 was exclusive to gliomas. This is the first report of TP53 gene polymorphism in glioma patients from India. Our study also delineates the frequency of four polymorphisms in gliomas for the first time. The codon 72 variant (rs1042522) and rs1642785 polymorphisms possibly poses risk to glioma development in Indian population. However, the functional significance of these polymorphism needs further elucidation. 相似文献
78.
Prasenjit Das Tarun Puri Vaishali Suri M. C. Sharma B. S. Sharma Chitra Sarkar 《Child's nervous system》2009,25(7):825-835
Background Medulloblastoma (MB) is the most common pediatric brain tumor. It is however rare in adults. The genetic and protein expression
profile of medulloblastoma is complex, which is worthwhile in terms of prognostication and development or selection of targeted
therapy.
Aims and objectives The aims and objectives to correlate the MIB-1 proliferation index and protein expression profiles of c-Myc, ERBB2, and anti-apoptotic
proteins (Bcl2 and Bcl-xL) in tumor cells with histological subtypes and clinical outcome.
Methods and material In 50 cases, histopathological subtyping was done, and protein expression profiling by immunohistochemical technique was performed
by stains for MIB-1, Bcl2, Bcl-xL, c-Myc, and ERBB2 in 30 cases. The findings were correlated with histological types and
patient’s average follow-up data.
Results Histological subtypes were similar to that described in literatures. The average expression of Bcl2, Bcl-xL, MIB-1, c-Myc,
and ERBB2 were as follows: 50.38%, 38.18%, 59.03%, 46.16%, and 59.62%, respectively. Bcl2 expression showed statistically
significant correlation with progress-free survival (PFS) [p = 0.046], while ERBB2 and MIB-1 showed a trend of higher expression in progressive disease. The protein expression pattern
did not correlate with histological subtypes.
Conclusion Though Bcl-2, ERBB2, and MIB-1 LI came out to be potential markers of aggressive behavior, c-Myc did not correlate with PFS
in MB. 相似文献
79.
Nadeem Tanveer Mehar C. Sharma Chitra Sarkar Sheffali Gulati Veena Kalra Sumit Singh Rohit Bhatia 《Clinical neurology and neurosurgery》2009
Aims
Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy.Methods
Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies.Results
Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%).Conclusion
Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy. 相似文献80.
Cooper DS Jacobs JP Moore L Stock A Gaynor JW Chancy T Parpard M Griffin DA Owens T Checchia PA Thiagarajan RR Spray TL Ravishankar C 《Cardiology in the young》2007,17(Z2):104-115
Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease.A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation.As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile "Berlin Heart" ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support "urgently" rather than "emergently", before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability. 相似文献