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排序方式: 共有4948条查询结果,搜索用时 15 毫秒
81.
Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors. 总被引:4,自引:0,他引:4
82.
Christopher R Gibson Charles Lin Rominder Singh Cheri M Brown Karen Richards Janice Brunner Kimberly Michel Jennifer Adelsberger Edward Carlini Catherine Boothe-Genthe Conrad Raab Minh Luu Aimee Michael Mona Parikh Patrice Ciecko Raju Subramanian Paul Krolikowski A David Rodrigues Thomas A Baillie Thomas H Rushmore 《Drug metabolism and disposition》2005,33(7):1044-1051
Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A. 相似文献
83.
Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans. 总被引:1,自引:0,他引:1
Thomas Frank Florian Conrad Stintzing Reinhold Carle Irmgard Bitsch Daniela Quaas Gabriele Strass Roland Bitsch Michael Netzel 《Pharmacological research》2005,52(4):290-297
The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile. 相似文献
84.
Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus of the dentate gyrus 总被引:6,自引:0,他引:6
The effects acute restraint stress on neuropeptide Y (NPY) mRNA expression were determined within the dentate gyrus and arcuate nucleus, where the effects of adrenal steroid action were previously reported. Adult male rats were exposed to 1 h of restraint stress and then sacrificed immediately, 6 h, or 24 h later. Controls were undisturbed. Stress increased NPY mRNA levels in both the arcuate nucleus and in the hilar region of the hippocampus with different time courses. NPY mRNA increased in the arcuate at 24 h, but not earlier, as determined by film autoradiography. Single cell grain analysis was performed in the dentate gyrus hilus because the NPY mRNA was heterogeneously distributed and revealed that the number of cells expressing NPY mRNA increased 6 h after stress, returning to control levels within 24 h. These results fit with previously reported effects of adrenal steroids modulating arcuate nucleus NPY expression through the adrenal steroid Type II receptors. In the hilus where adrenal steroid Type I receptors have been reported to suppress NPY mRNA levels, the effect of stress is in the opposite direction to that of adrenal steroid action and a more complex regulation of NPY expression is indicated. 相似文献
85.
86.
Synthesis and evaluation of a 18F‐labeled 4‐phenylpiperidine‐4‐carbonitrile radioligand for σ1 receptor imaging 下载免费PDF全文
Jiajun Ye Xia Wang Winnie Deuther‐Conrad Jinming Zhang Jianzhou Li Xiaojun Zhang Liang Wang Jörg Steinbach Peter Brust Hongmei Jia 《Journal of labelled compounds & radiopharmaceuticals》2016,59(9):332-339
We report the design and synthesis of several 4‐phenylpiperidine‐4‐carbonitrile derivatives as σ1 receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for σ1 receptors (Ki(σ1) = 1.22–2.14 nM) and extremely high subtype selectivity (Ki(σ2) = 830–1710 nM; Ki(σ2)/Ki(σ1) = 680–887). [18F]9 was prepared in 42–46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic 18F‐ substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain‐to‐blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [18F]9 significantly reduced the accumulation of radiotracers in organs known to contain σ1 receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [18F]9 may serve as a lead compound to develop suitable radiotracers for σ1 receptor imaging with positron emission tomography. 相似文献
87.
Yanis Merad Alexandre Gaymard Laurent Cotte Thomas Perpoint Dulce Alfaiate Matthieu Godinot Agathe Becker Olivier Cannesson Anne-Sophie Batalla Fatima Oria-Yassir Sophie Landr Florence Morfin Maude Bouscambert Florent Valour Florence Ader Anne Conrad 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(50)
Modified vaccinia virus Ankara vaccine (MVA-BN; Bavarian Nordic) is recommended to contacts of mpox cases up to 14 days post-exposure but the effectiveness of this strategy is unknown. Among 108 adults (≥ 18 years old) who received one dose of MVA-BN after exposure to mpox, 11 (10%) cases of breakthrough mpox were observed. Sexual exposure was associated with the risk of breakthrough mpox (p = 0.0179). Samples taken from vaccinated breakthrough mpox cases had similar rates of infectious virus isolation than unvaccinated mpox cases. 相似文献
88.
Vikas A. Gupta Shannon M. Matulis Benjamin G. Barwick R. Devin Bog Conrad W. Shebelut Mala Shanmugam Paola Neri Nizar J. Bahlis Madhav V. Dhodapkar Leonard T. Heffner Craig C. Hofmeister Nisha S. Joseph Sagar Lonial Jonathan L. Kaufman David L. Jaye Ajay K. Nooka Lawrence H. Boise 《Blood cancer journal》2022,12(8)
89.
R. Conrad 《International journal of pediatric otorhinolaryngology》1980,1(4):317-329
The early education of profoundly deaf children by largely oral means is still predominant world-wide. Essentially, the sensory deficit of these children is such that they are inevitably deprived of both auditory and linguistic input.Research on the effects of prolonged auditory deprivation in animals points strongly to the probability of transneuronal degeneration which may be irreversible, and it is argued that similar degeneration is likely in humans in the conditions accompanying profound congenital deafness. Furthermore, the homogeneity of central nervous system processes suggests that when the deprivation is linguistic, analogous damage may occur. An exclusive pedagogic insistence on speech in the presence of profound deafness risks providing appropriate conditions for disturbance of relevant neurological function. In these circumstances massive deficit of oral language development might be expected.Research involving almost every deaf school-leaver in England and Wales confirms this expectation. It shows the close dependence of degree of hearing-impairment on intelligibility of vocal speech. This in turn can be empirically shown to determine the likelihood of internalizing speech — of thinking orally. Lip-reading, aided by small amounts of residual hearing, is shown to be an extremely inefficient way of learning language, and penal degrees of reading retardation follow.The language deficit may be ameliorated if the inadequacies of the auditory system are supplemented by sign language used concurrently with speech, especially during the earliest years. This permits a deaf child to choose a language input appropriate to the level of his auditory functioning. 相似文献
90.
Klaus Conrad 《Journal of neurology》1948,159(1-2):132-187
Ohne ZusammenfassungMit 20 Textabbildungen (28 Einzelbildern). 相似文献