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51.
Germline p53 mutations are associated with cancer predisposition in Li-Fraumeni families as well as in individuals with component tumors of the syndrome. In the majority of cases these mutations have been shown to be inherited rather than de novo. We screened 59 children with primary bone or soft tissue sarcomas. Germline p53 mutations were identified in 2 patients. Interestingly, analysis revealed that both mutations were de novo. Although the frequency of germline p53 mutations in primary pediatric sarcoma patients is low, there is evidence for the importance of considering pediatric patients for testing for de novo mutations. 相似文献
52.
53.
In this report, we describe the clinical, topographical and immunohistochemical characteristics of neurofilament (NF) inclusion formation induced by the intracisternal inoculation of young adult New Zealand white rabbits at 28-day intervals with 100 g AlCl3 over the course of 267 days. The ability to recover following cessation of aluminum exposure has also been assessed. The extent of neurofilamentous inclusion formation was proportionate to the cumulative amount of AlCl3 inoculated and initially consisted of fusiform axonal distention in the ventral spinal cord at day 51 following the initial inoculum. Spinal motor neuron perikaryal inclusions and discrete axonal spheroids were observed at day 107 and supraspinal neurofilamentous pathology by day 156. Perikaryal inclusions were immunoreactive to antibodies recognizing both poorly phosphorylated (SMI 32) and more highly phosphorylated high molecular weight NF (NFH). In contrast, axonal spheroids were intensely immunoreactive at all stages with antibodies recognizing highly phosphorylated NFH and an age-dependent NFH phosphorylation state (SMI 34) with only faint SMI 32 immunoreactivity. Immunoreactivity to an antibody recognizing ubiquitin-protein conjugates did not appear until day 156, whereas inclusions were not immunoreactive to antibodies recognizing either phosphatase-dependent or-independent microtubule-associated protein tau at any stage. Upon withdrawal from further AlCl3 exposure after intervals of 51, 107 or 156 days following the initial inoculum, clinical recovery ensued in all rabbits. In all but the most severely affected rabbits, perikaryal neurofilamentous inclusions resolved. However, axonal spheroids continued to be prominent. However, axonal spheroids continued to be prominent. These studies demonstrate that the repetitive intracisternal inoculation of AlCl3 in New Zealand white rabbits induces a reversible process of neurofilamentous inclusion formation that preferentially affects motor neurons, and in which recovery will occur in those inclusions containing an admixture of both poorly and highly phosphorylated NFH. 相似文献
54.
Strong J Tooth L Unruh A 《Canadian journal of occupational therapy. Revue canadienne d'ergothérapie》1999,66(5):221-228
In recent years there has been a growing awareness amongst health professionals of the need to prepare undergraduate students more adequately for practice with clients who have pain. Occupational therapists have a central role in enabling such clients to have productive lives despite pain. In this study, an examination was made of the adequacy of preparation for pain practice in graduates from one Australian occupational therapy curriculum. Recent occupational therapy graduates from the University of Queensland, Australia, who responded to a postal survey, obtained an overall 53% correct response rate to a 69-item pain knowledge and attitudes questionnaire. Results indicated the need for further education in this area, especially in the areas of pharmacological management, and pain assessment and measurement. These results were comparable to those obtained from final year occupational therapy students at Dalhousie University in Halifax, Nova Scotia prior to undertaking an elective course about pain. Follow-up interviews with a number of new graduates supported the inclusion of an elective pain course in the undergraduate occupational therapy curriculum at the University of Queensland in Australia. 相似文献
55.
Kubota T Thomson A Clouston AD Nakazawa Y Steadman C Kerlin P Shimada H Balderson GA Lynch SV Strong RW 《Journal of Hepato-Biliary-Pancreatic Surgery》1999,6(4):377-381
Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because
the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical,
radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three
patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that
may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected
both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated
episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after
transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left
hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study
is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary
complications of the graft.
Received for publication on March 8, 1999; accepted on April 30, 1999 相似文献
56.
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR 总被引:8,自引:0,他引:8
Yang Yiping; Devor Daniel C.; Engelhardt John F.; Ernst Stephen A.; Strong Theresa V.; Collins Francis S.; Cohn Jonathan A.; Frizzell Raymond A.; Wilson James M. 《Human molecular genetics》1993,2(8):1253-1261
Cystic fibrosis (CF) is caused by mutations in the gene encodinga chloride channel called the CF transmembrane conductance regulator(CFTR). A single mutation in this gene, deletion of three nucleotidesthat leads to the absence of phenylalanine 508 (i.e., F508),is found on 70% of all CF chromosomes. To explore the molecularmechanism(s) responsible for defective chloride transport inpatients with CF, we have studied the processing, localization,and function of wild type (W.T.), F508 and G551D CFTR (a GDmissense mutation at position 551) in retrovirus transducedL cells. Cell transduced with W.T. CFTR expressed a 170 kd CFTRprotein that was endoglycosidase H (Endo H) resistant, localizedto the plasma membrane, and generated a cAMP-mediated anionconductance (GCl) when stimulated with standard concentrationsof forskolin (5 µM), cpt cAMP (400 µM) and IBMX(100 µM). The G551D CFTR was indistinguishable from W.T.CFTR with respect to post-translational processing and localization,but it did not produce a cAMP-activated GCI in response to thestandard stimulation cocktail. However, raising the IBMX concentrationto 4 mM produced Gc, in G551D expressing cells. Cells transducedwith F508 CFTR expressed an Endo H sensitive CFTR protein (140kd) that was found in a cytosolic, perinuclear location. Thesecells did not respond to the standard cocktail, but 20% of cellsincreased GCI when the cocktail contained 4 mM IBMX. Incubationof cells at 26°C for 48 hours prior to analysis elicitedresponses in F508 expressing cells at low IBMX concentrations,but had no effect on the responses of cells expressing W.T.or G551D CFTR. The response of F508 to 26°C was associatedwith plasma membrane localization of CFTR protein. These resultssuggest that there are two mechanisms whereby CFTR mutationslead to loss of cAMP-responsive GCI. First, shown by G551D CFTR,the protein can be processed and targeted to the plasma membranecorrectly, but lack full responsiveness to stimulation by cAMP.Second, as examplified by F508 CFTR, a partially functionalprotein which is not targeted to its correct cellular locationcan also lead to loss of the cAMP, responsive GCI. 相似文献
57.
58.
A series of 18 patients undergoing surgery for cerebellopontine angle tumors is reported. Patients were grouped according to size of tumor (0 to 2.5 cm, 11 cases; more than 2.5 cm, 7 cases). In all, the facial nerve was identified and conductance assessed by monitoring the facial electromyographic response to facial nerve stimulation. Postoperative facial nerve function was graded clinically after 3 months according to the House scale. Tumor removal was complete in all cases. In patients with tumors up to 2.5 cm the facial nerve was intact to visual inspection at the end of the procedure in all but one, where partial division was evident. In this group intraoperative facial nerve stimulation indicated electrical integrity in 8 of the 11 cases, all of which regained good facial nerve function postoperatively (House grades I and II). Nerve conduction was lost during the operation in the remaining three patients with small tumors; two subsequently developed a moderately severe (grade IV) dysfunction and the third, a total paralysis (grade VI). In the large (more than 2.5 cm) tumor group the facial nerve was anatomically intact in five of the seven cases, partially divided in one, and completely sectioned in the remaining case. Facial nerve stimulation indicated functional integrity in three patients, two of whom developed moderate (grade III) and the third a severe (grade V) dysfunction. In the other four cases nerve function could not be detected at operation; three of these developed a moderate facial nerve dysfunction (grade III/IV) and the final case a complete paralysis (grade VI). Intraoperative facial nerve monitoring appeared to predict eventual facial function accurately in the small tumor group, but did not predict facial nerve recovery reliably following surgery for larger tumors. 相似文献
59.
Adenoid cystic carcinoma: factors influencing survival. 总被引:10,自引:0,他引:10
We have reviewed our experience with 264 patients treated for adenoid cystic carcinoma of salivary origin. This study updates a previous report from our hospital and includes all patients treated during a 30 year period who were eligible for a minimum follow-up of 10 years. The tumor arose in minor salivary (mucous) glands in two thirds of the patients; half had received treatment elsewhere, and both sexes were equally represented. Actuarial survival curves and "cure" rates calculated by the direct method confirm that clinical staging provides a reliable prognostic guide. We are unable to demonstrate that the microscopic appearance of the tumor exerts a predictable effect on treatment results. Although some patients lived for many years after resection despite local recurrence and distant metastases, prolonged survival was unusual in patients with stage 3 lesions, particularly in those with sinus or submaxillary gland primaries. Based on the site of origin of the tumor and its clinical stage, it is now possible to select which patients with adenoid cystic carcinoma have the most ominous prognosis and perhaps plan a more appropriate operation. More importantly, these data may help focus on the subpopulation at greatest risk, which is vital to the design of any prospective study to assess the value of adjunctive irradiation and chemotherapy. 相似文献
60.
Robert C. Smith J. Randolph Strong Paul B. Hicks T. Samorajski 《Psychopharmacology》1979,60(3):241-246
Behavioral evidence for tolerance and supersensitivity during and after chronic (30 day) administration of bromocriptine (BRC) or bromocriptine + L-dopa in mice was assessed by measuring wheel running (WR) behavior during and after chronic drug administration, and apomorphine- and methylphenidate-(MP-) induced stereotyped gnawing after termination of chronic injections. In both BRC and BRC +L-dopa groups, tolerance developed fairly quickly to the depressing effect of BRC on WR seen on day 1 of drug administration. Mice receiving BRC showed significant increases in WR by week 2 of chronic drug administration, which persisted for at least two days after the termination of chronic injections. During the first week after termination of chronic injections, low doses of both apomorphine and MP induced significantly more stereotyped gnawing in BRC and BRC + L-dopa mice than in the control mice or the mice treated with L-dopa alone. This behavioral evidence for dopaminergic supersensitivity after chronic BRC administration may have relevance for the clinical use of BRC in combination with L-dopa or other dopamine agonists. 相似文献