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排序方式: 共有7140条查询结果,搜索用时 31 毫秒
151.
Antoinette R Tan Xiaowei Yang Stephen M Hewitt Arlene Berman Erin R Lepper Alex Sparreboom Allyson L Parr William D Figg Catherine Chow Seth M Steinberg Stephen L Bacharach Millie Whatley Jorge A Carrasquillo Jaime S Brahim Seth A Ettenberg Stan Lipkowitz Sandra M Swain 《Journal of clinical oncology》2004,22(15):3080-3090
PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients. 相似文献
152.
153.
Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer 总被引:2,自引:0,他引:2
Davidson LA; Aymond CM; Jiang YH; Turner ND; Lupton JR; Chapkin RS 《Carcinogenesis》1998,19(2):253-257
We have developed a non-invasive method utilizing feces, containing
sloughed colonocytes, as a sensitive technique for detecting diagnostic
colonic biomarkers. In this study, we used the rat colon carcinogenesis
model to determine if changes in fecal protein kinase C (PKC) expression
have predictive value in monitoring the neoplastic process. Weanling rats
were injected with saline or azoxymethane (AOM) and 36 weeks later fecal
samples and mucosa were collected, poly A+ RNA isolated, and quantitative
RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and
zeta mRNA levels were altered by the presence of a tumor, with
tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII
expression as compared with animals without tumors. In addition,
AOM-injection increased mucosal PKC betaII mRNA expression compared with
saline controls. No effect of tumor incidence on mucosal PKC betaII
expression was observed. In contrast, fecal PKC zeta expression was
2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus
saline. Since tumor incidence exerts a reciprocal effect on fecal PKC
betaII and zeta mRNA expression, data were also expressed as the ratio
between PKC betaII and zeta. The isozyme ratio was strongly related to
tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25,
animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that
the expression of fecal PKC betaII and zeta may serve as a noninvasive
marker for development of colon tumors. A sensitive technique for the
detection of colon cancer is of importance since early diagnosis can
substantially reduce mortality.
相似文献
154.
Beredjiklian PK Bozentka DJ Steinberg DR Bernstein J 《The Journal of bone and joint surgery. American volume》2000,(11):1540-1543
BACKGROUND: The Internet has become a popular source of medical information for patients. Authors of health-related web pages are not required to adhere to any standard for medical content or accuracy. The goal of the present study was to assess the type, quality, and reliability of information about carpal tunnel syndrome that is available on the Internet. METHODS: The search phrase "carpal tunnel syndrome" was entered into five commonly used World Wide Web search engines. The search results then were given as an ordered list of universal resource locators, or web-site addresses. The top (first) fifty web sites from each of the five searches were combined to create a master roster of 250 web-site addresses. These web sites then were evaluated for authorship and content, and an informational value score ranging from 0 to 100 points was assigned to each. RESULTS: Thirty-three percent of the sites sold commercial products for the evaluation or treatment of carpal tunnel syndrome. An additional 30 percent were commercial web sites that did not sell products. Only 23 percent of the sites were authored by a physician or an academic organization. Fewer than half of the sites offered conventional information. Twenty-three percent of the sites offered unconventional or misleading information. The mean informational value of the web sites was 28.4 of a possible 100 points. CONCLUSIONS: The information about carpal tunnel syndrome on the Internet is of limited quality and poor informational value. The public and the medical communities need to be aware of these limitations so that the quality of medical information available on the World Wide Web can be improved. 相似文献
155.
156.
Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases. 相似文献
157.
158.
159.
Stephan Mielke Alex Sparreboom Seth M Steinberg Hans Gelderblom Clemens Unger Dirk Behringer Klaus Mross 《Clinical cancer research》2005,11(13):4843-4850
PURPOSE: The shortening of infusion time from 3 to 1 hour decreases the systemic exposure (area under the curve, AUC) of total and unbound paclitaxel but increases the AUC of its vehicle Cremophor EL, whereas the time above total paclitaxel concentrations of 0.05 micromol/L (T >0.05) remains almost constant. As both Cremophor EL and paclitaxel are neurotoxic, we evaluated their pharmacodynamic effects on the development of peripheral neuropathy as the most important nonhematologic toxicity. EXPERIMENTAL DESIGN: Patients with advanced cancer of different origin were randomized to receive a maximum of 12 weekly-given 1- or 3-hour infusions of 100 mg/m2 paclitaxel (Taxol). Twenty-four patients were assessable for both pharmacokinetics and peripheral neuropathy development evaluated by a clinical scoring system including sensory symptoms, strength, tendon reflexes, and vibratory sense. RESULTS: Patients with peripheral neuropathy development (n=14) received more weeks of therapy (P=0.056) and showed significantly higher T(>0.05) (P=0.022) and overall systemic drug exposures (weeks of therapy x AUC) for total paclitaxel (P=0.002) and unbound paclitaxel (P=0.003) than those without peripheral neuropathy. In Kaplan-Meier analyses, T(>0.05) > or = 10.6 hours (P=0.023), AUC of total paclitaxel > or = 4.7 microg/mL x hour (P = 0.047), and AUC of unbound paclitaxel > or = 0.375 microg/mL x hour (P = 0.095) were identified as being potential factors for peripheral neuropathy development. In a Cox regression analysis, only T(>0.05) > or = 10.6 hours remained as an independent risk factor (relative risk, 18.43; P = 0.036) after adjusting for prior vincamycin (relative risk, 11.28; P = 0.038). CONCLUSIONS: From the results obtained in this study, it is concluded that exposure to paclitaxel but not Cremophor EL is associated with peripheral neuropathy development. 相似文献
160.
Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment 总被引:8,自引:0,他引:8
Baron AD Tarshoby M Hook G Lazaridis EN Cronin J Johnson A Steinberg HO 《Diabetes》2000,49(5):768-774
Insulin and glucose delivery (muscle perfusion) can modulate insulin-mediated glucose uptake. This study was undertaken to determine 1) to what extent insulin sensitivity modulates the effect of perfusion on glucose uptake and 2) whether this effect is achieved via capillary recruitment. We measured glucose disposal rates (GDRs) and leg muscle glucose uptake (LGU) in subjects exhibiting a wide range of insulin sensitivity, after 4 h of steady-state (SS) euglycemic hyperinsulinemia (>6,000 pmol/l) and subsequently after raising the rate of leg blood flow (LBF) 2-fold with a superimposed intrafemoral artery infusion of methacholine chloride (Mch), an endothelium-dependent vasodilator. LBF was determined by thermodilution: LGU = arteriovenous glucose difference (AVGdelta) x LBF. As a result of the 114+/-12% increase in LBF induced by Mch, the AVGdelta decreased 32+/-4%, and overall rates of LGU increased 40+/-5% (P < 0.05). We found a positive relationship between the Mch-modulated increase in LGU and insulin sensitivity (GDR) (r = 0.60, P < 0.02), suggesting that the most insulin-sensitive subjects had the greatest enhancement of LGU in response to augmentation of muscle perfusion. In separate groups of subjects, we also examined the relationship between muscle perfusion rate and glucose extraction (AVGdelta). Perfusion was either pharmacologically enhanced with Mch or reduced by intra-arterial infusion of the nitric oxide inhibitor N(G)-monomethyl-L-arginine during SS euglycemic hyperinsulinemia. Over the range of LBF, changes in AVGdelta were smaller than expected based on the noncapillary recruitment model of Renkin. Together, the data indicate that 1) muscle perfusion becomes more rate limiting to glucose uptake as insulin sensitivity increases and 2) insulin-mediated increments in muscle perfusion are accompanied by capillary recruitment. Thus, insulin-stimulated glucose uptake displays both permeability- and perfusion-limited glucose exchange properties. 相似文献